ALBERT

Description: Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified 〉300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235490/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235490/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International HIV Controllers Study -- Pereyra, Florencia -- Jia, Xiaoming -- McLaren, Paul J -- Telenti, Amalio -- de Bakker, Paul I W -- Walker, Bruce D -- Ripke, Stephan -- Brumme, Chanson J -- Pulit, Sara L -- Carrington, Mary -- Kadie, Carl M -- Carlson, Jonathan M -- Heckerman, David -- Graham, Robert R -- Plenge, Robert M -- Deeks, Steven G -- Gianniny, Lauren -- Crawford, Gabriel -- Sullivan, Jordan -- Gonzalez, Elena -- Davies, Leela -- Camargo, Amy -- Moore, Jamie M -- Beattie, Nicole -- Gupta, Supriya -- Crenshaw, Andrew -- Burtt, Noel P -- Guiducci, Candace -- Gupta, Namrata -- Gao, Xiaojiang -- Qi, Ying -- Yuki, Yuko -- Piechocka-Trocha, Alicja -- Cutrell, Emily -- Rosenberg, Rachel -- Moss, Kristin L -- Lemay, Paul -- O'Leary, Jessica -- Schaefer, Todd -- Verma, Pranshu -- Toth, Ildiko -- Block, Brian -- Baker, Brett -- Rothchild, Alissa -- Lian, Jeffrey -- Proudfoot, Jacqueline -- Alvino, Donna Marie L -- Vine, Seanna -- Addo, Marylyn M -- Allen, Todd M -- Altfeld, Marcus -- Henn, Matthew R -- Le Gall, Sylvie -- Streeck, Hendrik -- Haas, David W -- Kuritzkes, Daniel R -- Robbins, Gregory K -- Shafer, Robert W -- Gulick, Roy M -- Shikuma, Cecilia M -- Haubrich, Richard -- Riddler, Sharon -- Sax, Paul E -- Daar, Eric S -- Ribaudo, Heather J -- Agan, Brian -- Agarwal, Shanu -- Ahern, Richard L -- Allen, Brady L -- Altidor, Sherly -- Altschuler, Eric L -- Ambardar, Sujata -- Anastos, Kathryn -- Anderson, Ben -- Anderson, Val -- Andrady, Ushan -- Antoniskis, Diana -- Bangsberg, David -- Barbaro, Daniel -- Barrie, William -- Bartczak, J -- Barton, Simon -- Basden, Patricia -- Basgoz, Nesli -- Bazner, Suzane -- Bellos, Nicholaos C -- Benson, Anne M -- Berger, Judith -- Bernard, Nicole F -- Bernard, Annette M -- Birch, Christopher -- Bodner, Stanley J -- Bolan, Robert K -- Boudreaux, Emilie T -- Bradley, Meg -- Braun, James F -- Brndjar, Jon E -- Brown, Stephen J -- Brown, Katherine -- Brown, Sheldon T -- Burack, Jedidiah -- Bush, Larry M -- Cafaro, Virginia -- Campbell, Omobolaji -- Campbell, John -- Carlson, Robert H -- Carmichael, J Kevin -- Casey, Kathleen K -- Cavacuiti, Chris -- Celestin, Gregory -- Chambers, Steven T -- Chez, Nancy -- Chirch, Lisa M -- Cimoch, Paul J -- Cohen, Daniel -- Cohn, Lillian E -- Conway, Brian -- Cooper, David A -- Cornelson, Brian -- Cox, David T -- Cristofano, Michael V -- Cuchural, George Jr -- Czartoski, Julie L -- Dahman, Joseph M -- Daly, Jennifer S -- Davis, Benjamin T -- Davis, Kristine -- Davod, Sheila M -- DeJesus, Edwin -- Dietz, Craig A -- Dunham, Eleanor -- Dunn, Michael E -- Ellerin, Todd B -- Eron, Joseph J -- Fangman, John J W -- Farel, Claire E -- Ferlazzo, Helen -- Fidler, Sarah -- Fleenor-Ford, Anita -- Frankel, Renee -- Freedberg, Kenneth A -- French, Neel K -- Fuchs, Jonathan D -- Fuller, Jon D -- Gaberman, Jonna -- Gallant, Joel E -- Gandhi, Rajesh T -- Garcia, Efrain -- Garmon, Donald -- Gathe, Joseph C Jr -- Gaultier, Cyril R -- Gebre, Wondwoosen -- Gilman, Frank D -- Gilson, Ian -- Goepfert, Paul A -- Gottlieb, Michael S -- Goulston, Claudia -- Groger, Richard K -- Gurley, T Douglas -- Haber, Stuart -- Hardwicke, Robin -- Hardy, W David -- Harrigan, P Richard -- Hawkins, Trevor N -- Heath, Sonya -- Hecht, Frederick M -- Henry, W Keith -- Hladek, Melissa -- Hoffman, Robert P -- Horton, James M -- Hsu, Ricky K -- Huhn, Gregory D -- Hunt, Peter -- Hupert, Mark J -- Illeman, Mark L -- Jaeger, Hans -- Jellinger, Robert M -- John, Mina -- Johnson, Jennifer A -- Johnson, Kristin L -- Johnson, Heather -- Johnson, Kay -- Joly, Jennifer -- Jordan, Wilbert C -- Kauffman, Carol A -- Khanlou, Homayoon -- Killian, Robert K -- Kim, Arthur Y -- Kim, David D -- Kinder, Clifford A -- Kirchner, Jeffrey T -- Kogelman, Laura -- Kojic, Erna Milunka -- Korthuis, P Todd -- Kurisu, Wayne -- Kwon, Douglas S -- LaMar, Melissa -- Lampiris, Harry -- Lanzafame, Massimiliano -- Lederman, Michael M -- Lee, David M -- Lee, Jean M L -- Lee, Marah J -- Lee, Edward T Y -- Lemoine, Janice -- Levy, Jay A -- Llibre, Josep M -- Liguori, Michael A -- Little, Susan J -- Liu, Anne Y -- Lopez, Alvaro J -- Loutfy, Mono R -- Loy, Dawn -- Mohammed, Debbie Y -- Man, Alan -- Mansour, Michael K -- Marconi, Vincent C -- Markowitz, Martin -- Marques, Rui -- Martin, Jeffrey N -- Martin, Harold L Jr -- Mayer, Kenneth Hugh -- McElrath, M Juliana -- McGhee, Theresa A -- McGovern, Barbara H -- McGowan, Katherine -- McIntyre, Dawn -- Mcleod, Gavin X -- Menezes, Prema -- Mesa, Greg -- Metroka, Craig E -- Meyer-Olson, Dirk -- Miller, Andy O -- Montgomery, Kate -- Mounzer, Karam C -- Nagami, Ellen H -- Nagin, Iris -- Nahass, Ronald G -- Nelson, Margret O -- Nielsen, Craig -- Norene, David L -- O'Connor, David H -- Ojikutu, Bisola O -- Okulicz, Jason -- Oladehin, Olakunle O -- Oldfield, Edward C 3rd -- Olender, Susan A -- Ostrowski, Mario -- Owen, William F Jr -- Pae, Eunice -- Parsonnet, Jeffrey -- Pavlatos, Andrew M -- Perlmutter, Aaron M -- Pierce, Michael N -- Pincus, Jonathan M -- Pisani, Leandro -- Price, Lawrence Jay -- Proia, Laurie -- Prokesch, Richard C -- Pujet, Heather Calderon -- Ramgopal, Moti -- Rathod, Almas -- Rausch, Michael -- Ravishankar, J -- Rhame, Frank S -- Richards, Constance Shamuyarira -- Richman, Douglas D -- Rodes, Berta -- Rodriguez, Milagros -- Rose, Richard C 3rd -- Rosenberg, Eric S -- Rosenthal, Daniel -- Ross, Polly E -- Rubin, David S -- Rumbaugh, Elease -- Saenz, Luis -- Salvaggio, Michelle R -- Sanchez, William C -- Sanjana, Veeraf M -- Santiago, Steven -- Schmidt, Wolfgang -- Schuitemaker, Hanneke -- Sestak, Philip M -- Shalit, Peter -- Shay, William -- Shirvani, Vivian N -- Silebi, Vanessa I -- Sizemore, James M Jr -- Skolnik, Paul R -- Sokol-Anderson, Marcia -- Sosman, James M -- Stabile, Paul -- Stapleton, Jack T -- Starrett, Sheree -- Stein, Francine -- Stellbrink, Hans-Jurgen -- Sterman, F Lisa -- Stone, Valerie E -- Stone, David R -- Tambussi, Giuseppe -- Taplitz, Randy A -- Tedaldi, Ellen M -- Theisen, William -- Torres, Richard -- Tosiello, Lorraine -- Tremblay, Cecile -- Tribble, Marc A -- Trinh, Phuong D -- Tsao, Alice -- Ueda, Peggy -- Vaccaro, Anthony -- Valadas, Emilia -- Vanig, Thanes J -- Vecino, Isabel -- Vega, Vilma M -- Veikley, Wenoah -- Wade, Barbara H -- Walworth, Charles -- Wanidworanun, Chingchai -- Ward, Douglas J -- Warner, Daniel A -- Weber, Robert D -- Webster, Duncan -- Weis, Steve -- Wheeler, David A -- White, David J -- Wilkins, Ed -- Winston, Alan -- Wlodaver, Clifford G -- van't Wout, Angelique -- Wright, David P -- Yang, Otto O -- Yurdin, David L -- Zabukovic, Brandon W -- Zachary, Kimon C -- Zeeman, Beth -- Zhao, Meng -- AI030914/AI/NIAID NIH HHS/ -- AI068636/AI/NIAID NIH HHS/ -- AI069415/AI/NIAID NIH HHS/ -- AI069419/AI/NIAID NIH HHS/ -- AI069423/AI/NIAID NIH HHS/ -- AI069424/AI/NIAID NIH HHS/ -- AI069428/AI/NIAID NIH HHS/ -- AI069432/AI/NIAID NIH HHS/ -- AI069434/AI/NIAID NIH HHS/ -- AI069450/AI/NIAID NIH HHS/ -- AI069452/AI/NIAID NIH HHS/ -- AI069465/AI/NIAID NIH HHS/ -- AI069471/AI/NIAID NIH HHS/ -- AI069472/AI/NIAID NIH HHS/ -- AI069474/AI/NIAID NIH HHS/ -- AI069477/AI/NIAID NIH HHS/ -- AI069484/AI/NIAID NIH HHS/ -- AI069495/AI/NIAID NIH HHS/ -- AI069501/AI/NIAID NIH HHS/ -- AI069502/AI/NIAID NIH HHS/ -- AI069511/AI/NIAID NIH HHS/ -- AI069513/AI/NIAID NIH HHS/ -- AI069532/AI/NIAID NIH HHS/ -- AI069556/AI/NIAID NIH HHS/ -- AI077505/AI/NIAID NIH HHS/ -- AI087145/AI/NIAID NIH HHS/ -- AI25859/AI/NIAID NIH HHS/ -- AI27661/AI/NIAID NIH HHS/ -- AI28568/AI/NIAID NIH HHS/ -- AI30914/AI/NIAID NIH HHS/ -- AI34835/AI/NIAID NIH HHS/ -- AI34853/AI/NIAID NIH HHS/ -- AI38844/AI/NIAID NIH HHS/ -- AI46370/AI/NIAID NIH HHS/ -- AI68634/AI/NIAID NIH HHS/ -- AI69467/AI/NIAID NIH HHS/ -- AL32782/PHS HHS/ -- HHSN261200800001E/PHS HHS/ -- K23 DA019809/DA/NIDA NIH HHS/ -- K24 AI051966/AI/NIAID NIH HHS/ -- K24 AI064086/AI/NIAID NIH HHS/ -- K24 AI064086-05/AI/NIAID NIH HHS/ -- K24 AI069994/AI/NIAID NIH HHS/ -- K24 AI069994-04/AI/NIAID NIH HHS/ -- K24 AI069994-05/AI/NIAID NIH HHS/ -- K24AI069994/AI/NIAID NIH HHS/ -- KL2 RR024977/RR/NCRR NIH HHS/ -- MH071205/MH/NIMH NIH HHS/ -- MH085520/MH/NIMH NIH HHS/ -- P-30 AI27763/AI/NIAID NIH HHS/ -- P-30-AI060354/AI/NIAID NIH HHS/ -- P30 AI027763/AI/NIAID NIH HHS/ -- P30 AI027763-19/AI/NIAID NIH HHS/ -- P30 AI027763-20/AI/NIAID NIH HHS/ -- P30 AI050410/AI/NIAID NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- P30 AI060354-08/AI/NIAID NIH HHS/ -- P30 AI060354-09/AI/NIAID NIH HHS/ -- 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HHS/ -- U01 AI069484-06/AI/NIAID NIH HHS/ -- U01 AI069495/AI/NIAID NIH HHS/ -- U01 AI069495-05/AI/NIAID NIH HHS/ -- U01 AI069495-06/AI/NIAID NIH HHS/ -- U01 AI069501/AI/NIAID NIH HHS/ -- U01 AI069501-05/AI/NIAID NIH HHS/ -- U01 AI069501-06/AI/NIAID NIH HHS/ -- U01 AI069502/AI/NIAID NIH HHS/ -- U01 AI069502-05/AI/NIAID NIH HHS/ -- U01 AI069502-06/AI/NIAID NIH HHS/ -- U01 AI069511/AI/NIAID NIH HHS/ -- U01 AI069511-05/AI/NIAID NIH HHS/ -- U01 AI069511-06/AI/NIAID NIH HHS/ -- U01 AI069513-05/AI/NIAID NIH HHS/ -- U01 AI069513-06/AI/NIAID NIH HHS/ -- U01 AI069532/AI/NIAID NIH HHS/ -- U01 AI069532-05/AI/NIAID NIH HHS/ -- U01 AI069532-06/AI/NIAID NIH HHS/ -- U01 AI069556-05/AI/NIAID NIH HHS/ -- U01 AI069556-06/AI/NIAID NIH HHS/ -- U01 MH085520/MH/NIMH NIH HHS/ -- U01 MH085520-01/MH/NIMH NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- UL1 RR024131-06/RR/NCRR NIH HHS/ -- UL1 RR024131-07/RR/NCRR NIH HHS/ -- UL1 RR024975/RR/NCRR NIH HHS/ -- UL1 RR024975-04/RR/NCRR NIH HHS/ -- UL1 RR024975-05/RR/NCRR NIH HHS/ -- UM1 AI068634/AI/NIAID NIH HHS/ -- UM1 AI068634-06/AI/NIAID NIH HHS/ -- UM1 AI068634-07/AI/NIAID NIH HHS/ -- UM1 AI068636-06/AI/NIAID NIH HHS/ -- UM1 AI068636-07/AI/NIAID NIH HHS/ -- UM1 AI069477/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1551-7. doi: 10.1126/science.1195271. Epub 2010 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology (MIT) and Harvard, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051598" target="_blank"〉PubMed〈/a〉

Description: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (〉/=140 mm Hg systolic blood pressure or 〉/=90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340926/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340926/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Consortium for Blood Pressure Genome-Wide Association Studies -- Ehret, Georg B -- Munroe, Patricia B -- Rice, Kenneth M -- Bochud, Murielle -- Johnson, Andrew D -- Chasman, Daniel I -- Smith, Albert V -- Tobin, Martin D -- Verwoert, Germaine C -- Hwang, Shih-Jen -- Pihur, Vasyl -- Vollenweider, Peter -- O'Reilly, Paul F -- Amin, Najaf -- Bragg-Gresham, Jennifer L -- Teumer, Alexander -- Glazer, Nicole L -- Launer, Lenore -- Zhao, Jing Hua -- Aulchenko, Yurii -- Heath, Simon -- Sober, Siim -- Parsa, Afshin -- Luan, Jian'an -- Arora, Pankaj -- Dehghan, Abbas -- Zhang, Feng -- Lucas, Gavin -- Hicks, Andrew A -- Jackson, Anne U -- Peden, John F -- Tanaka, Toshiko -- Wild, Sarah H -- Rudan, Igor -- Igl, Wilmar -- Milaneschi, Yuri -- Parker, Alex N -- Fava, Cristiano -- Chambers, John C -- Fox, Ervin R -- Kumari, Meena -- Go, Min Jin -- van der Harst, Pim -- Kao, Wen Hong Linda -- Sjogren, Marketa -- Vinay, D G -- Alexander, Myriam -- Tabara, Yasuharu -- Shaw-Hawkins, Sue -- Whincup, Peter H -- Liu, Yongmei -- Shi, Gang -- Kuusisto, Johanna -- Tayo, Bamidele -- Seielstad, Mark -- Sim, Xueling -- Nguyen, Khanh-Dung Hoang -- Lehtimaki, Terho -- Matullo, Giuseppe -- Wu, Ying -- Gaunt, Tom R -- Onland-Moret, N Charlotte -- Cooper, Matthew N -- Platou, Carl G P -- Org, Elin -- Hardy, Rebecca -- Dahgam, Santosh -- Palmen, Jutta -- Vitart, Veronique -- Braund, Peter S -- Kuznetsova, Tatiana -- Uiterwaal, Cuno S P M -- Adeyemo, Adebowale -- Palmas, Walter -- Campbell, Harry -- Ludwig, Barbara -- Tomaszewski, Maciej -- Tzoulaki, Ioanna -- Palmer, Nicholette D -- CARDIoGRAM consortium -- CKDGen Consortium -- KidneyGen Consortium -- EchoGen consortium -- CHARGE-HF consortium -- Aspelund, Thor -- Garcia, Melissa -- Chang, Yen-Pei C -- O'Connell, Jeffrey R -- Steinle, Nanette I -- Grobbee, Diederick E -- Arking, Dan E -- Kardia, Sharon L -- Morrison, Alanna C -- Hernandez, Dena -- Najjar, Samer -- McArdle, Wendy L -- Hadley, David -- Brown, Morris J -- Connell, John M -- Hingorani, Aroon D -- Day, Ian N M -- Lawlor, Debbie A -- Beilby, John P -- Lawrence, Robert W -- Clarke, Robert -- Hopewell, Jemma C -- Ongen, Halit -- Dreisbach, Albert W -- Li, Yali -- Young, J Hunter -- Bis, Joshua C -- Kahonen, Mika -- Viikari, Jorma -- Adair, Linda S -- Lee, Nanette R -- Chen, Ming-Huei -- Olden, Matthias -- Pattaro, Cristian -- Bolton, Judith A Hoffman -- Kottgen, Anna -- Bergmann, Sven -- Mooser, Vincent -- Chaturvedi, Nish -- Frayling, Timothy M -- Islam, Muhammad -- Jafar, Tazeen H -- Erdmann, Jeanette -- Kulkarni, Smita R -- Bornstein, Stefan R -- Grassler, Jurgen -- Groop, Leif -- Voight, Benjamin F -- Kettunen, Johannes -- Howard, Philip -- Taylor, Andrew -- Guarrera, Simonetta -- Ricceri, Fulvio -- Emilsson, Valur -- Plump, Andrew -- Barroso, Ines -- Khaw, Kay-Tee -- Weder, Alan B -- Hunt, Steven C -- Sun, Yan V -- Bergman, Richard N -- Collins, Francis S -- Bonnycastle, Lori L -- Scott, Laura J -- Stringham, Heather M -- Peltonen, Leena -- Perola, Markus -- Vartiainen, Erkki -- Brand, Stefan-Martin -- Staessen, Jan A -- Wang, Thomas J -- Burton, Paul R -- Soler Artigas, Maria -- Dong, Yanbin -- Snieder, Harold -- Wang, Xiaoling -- Zhu, Haidong -- Lohman, Kurt K -- Rudock, Megan E -- Heckbert, Susan R -- Smith, Nicholas L -- Wiggins, Kerri L -- Doumatey, Ayo -- Shriner, Daniel -- Veldre, Gudrun -- Viigimaa, Margus -- Kinra, Sanjay -- Prabhakaran, Dorairaj -- Tripathy, Vikal -- Langefeld, Carl D -- Rosengren, Annika -- Thelle, Dag S -- Corsi, Anna Maria -- Singleton, Andrew -- Forrester, Terrence -- Hilton, Gina -- McKenzie, Colin A -- Salako, Tunde -- Iwai, Naoharu -- Kita, Yoshikuni -- Ogihara, Toshio -- Ohkubo, Takayoshi -- Okamura, Tomonori -- Ueshima, Hirotsugu -- Umemura, Satoshi -- Eyheramendy, Susana -- Meitinger, Thomas -- Wichmann, H-Erich -- Cho, Yoon Shin -- Kim, Hyung-Lae -- Lee, Jong-Young -- Scott, James -- Sehmi, Joban S -- Zhang, Weihua -- Hedblad, Bo -- Nilsson, Peter -- Smith, George Davey -- Wong, Andrew -- Narisu, Narisu -- Stancakova, Alena -- Raffel, Leslie J -- Yao, Jie -- Kathiresan, Sekar -- O'Donnell, Christopher J -- Schwartz, Stephen M -- Ikram, M Arfan -- Longstreth, W T Jr -- Mosley, Thomas H -- Seshadri, Sudha -- Shrine, Nick R G -- Wain, Louise V -- Morken, Mario A -- Swift, Amy J -- Laitinen, Jaana -- Prokopenko, Inga -- Zitting, Paavo -- Cooper, Jackie A -- Humphries, Steve E -- Danesh, John -- Rasheed, Asif -- Goel, Anuj -- Hamsten, Anders -- Watkins, Hugh -- Bakker, Stephan J L -- van Gilst, Wiek H -- Janipalli, Charles S -- Mani, K Radha -- Yajnik, Chittaranjan S -- Hofman, Albert -- Mattace-Raso, Francesco U S -- Oostra, Ben A -- Demirkan, Ayse -- Isaacs, Aaron -- Rivadeneira, Fernando -- Lakatta, Edward G -- Orru, Marco -- Scuteri, Angelo -- Ala-Korpela, Mika -- Kangas, Antti J -- Lyytikainen, Leo-Pekka -- Soininen, Pasi -- Tukiainen, Taru -- Wurtz, Peter -- Ong, Rick Twee-Hee -- Dorr, Marcus -- Kroemer, Heyo K -- Volker, Uwe -- Volzke, Henry -- Galan, Pilar -- Hercberg, Serge -- Lathrop, Mark -- Zelenika, Diana -- Deloukas, Panos -- Mangino, Massimo -- Spector, Tim D -- Zhai, Guangju -- Meschia, James F -- Nalls, Michael A -- Sharma, Pankaj -- Terzic, Janos -- Kumar, M V Kranthi -- Denniff, Matthew -- Zukowska-Szczechowska, Ewa -- Wagenknecht, Lynne E -- Fowkes, F Gerald R -- Charchar, Fadi J -- Schwarz, Peter E H -- Hayward, Caroline -- Guo, Xiuqing -- Rotimi, Charles -- Bots, Michiel L -- Brand, Eva -- Samani, Nilesh J -- Polasek, Ozren -- Talmud, Philippa J -- Nyberg, Fredrik -- Kuh, Diana -- Laan, Maris -- Hveem, Kristian -- Palmer, Lyle J -- van der Schouw, Yvonne T -- Casas, Juan P -- Mohlke, Karen L -- Vineis, Paolo -- Raitakari, Olli -- Ganesh, Santhi K -- Wong, Tien Y -- Tai, E Shyong -- Cooper, Richard S -- Laakso, Markku -- Rao, Dabeeru C -- Harris, Tamara B -- Morris, Richard W -- Dominiczak, Anna F -- Kivimaki, Mika -- Marmot, Michael G -- Miki, Tetsuro -- Saleheen, Danish -- Chandak, Giriraj R -- Coresh, Josef -- Navis, Gerjan -- Salomaa, Veikko -- Han, Bok-Ghee -- Zhu, Xiaofeng -- Kooner, Jaspal S -- Melander, Olle -- Ridker, Paul M -- Bandinelli, Stefania -- Gyllensten, Ulf B -- Wright, Alan F -- Wilson, James F -- Ferrucci, Luigi -- Farrall, Martin -- Tuomilehto, Jaakko -- Pramstaller, Peter P -- Elosua, Roberto -- Soranzo, Nicole -- Sijbrands, Eric J G -- Altshuler, David -- Loos, Ruth J F -- Shuldiner, Alan R -- Gieger, Christian -- Meneton, Pierre -- Uitterlinden, Andre G -- Wareham, Nicholas J -- Gudnason, Vilmundur -- Rotter, Jerome I -- Rettig, Rainer -- Uda, Manuela -- Strachan, David P -- Witteman, Jacqueline C M -- Hartikainen, Anna-Liisa -- Beckmann, Jacques S -- Boerwinkle, Eric -- Vasan, Ramachandran S -- Boehnke, Michael -- Larson, Martin G -- Jarvelin, Marjo-Riitta -- Psaty, Bruce M -- Abecasis, Goncalo R -- Chakravarti, Aravinda -- Elliott, Paul -- van Duijn, Cornelia M -- Newton-Cheh, Christopher -- Levy, Daniel -- Caulfield, Mark J -- Johnson, Toby -- 068545/Z/02/Wellcome Trust/United Kingdom -- 070191/Z/03/Z/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 080747/Z/06/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 1R01AG032098-01A/AG/NIA NIH HHS/ -- 1RL1MH083268-01/MH/NIMH NIH HHS/ -- 263 MD 821336/MD/NIMHD NIH HHS/ -- 263 MD 9164/MD/NIMHD NIH HHS/ -- 263-MA-410953/PHS HHS/ -- 2M01RR010284/RR/NCRR NIH 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-- G0501942/Medical Research Council/United Kingdom -- G0600331/Medical Research Council/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- G0601966/Medical Research Council/United Kingdom -- G0700931/Medical Research Council/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G0902037/Medical Research Council/United Kingdom -- G0902313/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- G19/35/Medical Research Council/United Kingdom -- G20234/Biotechnology and Biological Sciences Research Council/United Kingdom -- G8802774/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- G9521010D/Medical Research Council/United Kingdom -- HG003054/HG/NHGRI NIH HHS/ -- HG005581/HG/NHGRI NIH HHS/ -- HHSN268200625226C/PHS HHS/ -- HHSN268200782096/PHS HHS/ -- HHSN268200782096C/PHS HHS/ -- HL 54512/HL/NHLBI NIH HHS/ -- HL-87660/HL/NHLBI NIH HHS/ -- HL043851/HL/NHLBI NIH HHS/ -- HL080025/HL/NHLBI NIH HHS/ -- HL084729/HL/NHLBI NIH HHS/ -- HL085144/HL/NHLBI NIH HHS/ -- HL086718/HL/NHLBI NIH HHS/ -- HL087647/HL/NHLBI NIH HHS/ -- HL098283/HL/NHLBI NIH HHS/ -- HL36310/HL/NHLBI NIH HHS/ -- HL45508/HL/NHLBI NIH HHS/ -- HL53353/HL/NHLBI NIH HHS/ -- HL54512/HL/NHLBI NIH HHS/ -- HS06516/HS/AHRQ HHS/ -- K12RR023250/RR/NCRR NIH HHS/ -- M01 RR16500/RR/NCRR NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- MC_PC_U127561128/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- MC_U123092720/Medical Research Council/United Kingdom -- MC_U123092723/Medical Research Council/United Kingdom -- MC_U127561128/Medical Research Council/United Kingdom -- MC_U137686857/Medical Research Council/United Kingdom -- MC_UP_A100_1003/Medical Research Council/United Kingdom -- MOP-82810/Canadian Institutes of Health Research/Canada -- MOP172605/Canadian Institutes of Health Research/Canada -- MOP77682/Canadian Institutes of Health Research/Canada -- N01 HC-15103/HC/NHLBI NIH HHS/ -- N01 HC-55222/HC/NHLBI NIH HHS/ -- N01 HC-95159/HC/NHLBI NIH HHS/ -- N01 HC-95169/HC/NHLBI NIH HHS/ -- N01-AG-1-2109/AG/NIA NIH HHS/ -- N01-AG-12100/AG/NIA NIH HHS/ -- N01-HC-25195/HC/NHLBI NIH HHS/ -- N01-HC-35129/HC/NHLBI NIH HHS/ -- N01-HC-45133/HC/NHLBI NIH HHS/ -- N01-HC-55015/HC/NHLBI NIH HHS/ -- N01-HC-55016/HC/NHLBI NIH HHS/ -- N01-HC-55018/HC/NHLBI NIH HHS/ -- N01-HC-55019/HC/NHLBI NIH HHS/ -- N01-HC-55020/HC/NHLBI NIH HHS/ -- N01-HC-55021/HC/NHLBI NIH HHS/ -- N01-HC-55022/HC/NHLBI NIH HHS/ -- N01-HC-75150/HC/NHLBI NIH HHS/ -- N01-HC-85079/HC/NHLBI NIH HHS/ -- N01-HC-85080/HC/NHLBI NIH HHS/ -- N01-HC-85081/HC/NHLBI NIH HHS/ -- N01-HC-85082/HC/NHLBI NIH HHS/ -- N01-HC-85083/HC/NHLBI NIH HHS/ -- N01-HC-85084/HC/NHLBI NIH HHS/ -- N01-HC-85085/HC/NHLBI NIH HHS/ -- N01-HC-85086/HC/NHLBI NIH HHS/ -- N01-HC-95160/HC/NHLBI NIH HHS/ -- 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HL086694-04A1/HL/NHLBI NIH HHS/ -- R01 HL086694-05/HL/NHLBI NIH HHS/ -- R01 HL087647/HL/NHLBI NIH HHS/ -- R01 HL087652/HL/NHLBI NIH HHS/ -- R01 HL088119/HL/NHLBI NIH HHS/ -- R01 NS39987/NS/NINDS NIH HHS/ -- R01 NS42733/NS/NINDS NIH HHS/ -- R01DK058845/DK/NIDDK NIH HHS/ -- R01DK066574/DK/NIDDK NIH HHS/ -- R01HL056931/HL/NHLBI NIH HHS/ -- R01HL060894/HL/NHLBI NIH HHS/ -- R01HL060919/HL/NHLBI NIH HHS/ -- R01HL06094/HL/NHLBI NIH HHS/ -- R01HL061019/HL/NHLBI NIH HHS/ -- R01HL071051/HL/NHLBI NIH HHS/ -- R01HL071205/HL/NHLBI NIH HHS/ -- R01HL071250/HL/NHLBI NIH HHS/ -- R01HL071251/HL/NHLBI NIH HHS/ -- R01HL071252/HL/NHLBI NIH HHS/ -- R01HL071258/HL/NHLBI NIH HHS/ -- R01HL071259/HL/NHLBI NIH HHS/ -- R01HL086694/HL/NHLBI NIH HHS/ -- R01HL087641/HL/NHLBI NIH HHS/ -- R01HL089650-02/HL/NHLBI NIH HHS/ -- R01HL59367/HL/NHLBI NIH HHS/ -- R03 TW007165/TW/FIC NIH HHS/ -- R37HL051021/HL/NHLBI NIH HHS/ -- RG/07/005/23633/British Heart Foundation/United Kingdom -- RG/07/008/23674/British Heart Foundation/United Kingdom -- RG/08/008/25291/British Heart Foundation/United Kingdom -- RG/08/013/25942/British Heart Foundation/United Kingdom -- RG/08/014/24067/British Heart Foundation/United Kingdom -- RG/98002/British Heart Foundation/United Kingdom -- RG08/01/British Heart Foundation/United Kingdom -- RR-024156/RR/NCRR NIH HHS/ -- RR20649/RR/NCRR NIH HHS/ -- S06GM008016-320107/GM/NIGMS NIH HHS/ -- S06GM008016-380111/GM/NIGMS NIH HHS/ -- SP/04/002/British Heart Foundation/United Kingdom -- SP/08/005/25115/British Heart Foundation/United Kingdom -- TW008288/TW/FIC NIH HHS/ -- TW05596/TW/FIC NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 GM074518-04/GM/NIGMS NIH HHS/ -- U01 HL054466/HL/NHLBI NIH HHS/ -- U01 HL054466-11/HL/NHLBI NIH HHS/ -- U01 HL054471/HL/NHLBI NIH HHS/ -- U01 HL054473/HL/NHLBI NIH HHS/ -- U01 HL054527/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 NS069208/NS/NINDS NIH HHS/ -- U01 NS069208-01/NS/NINDS NIH HHS/ -- U01DE018903/DE/NIDCR NIH HHS/ -- U01DE01899/DE/NIDCR NIH HHS/ -- U01HG004399/HG/NHGRI NIH HHS/ -- U01HG004402/HG/NHGRI NIH HHS/ -- U01HG004415/HG/NHGRI NIH HHS/ -- U01HG004422/HG/NHGRI NIH HHS/ -- U01HG004423/HG/NHGRI NIH HHS/ -- U01HG004436/HG/NHGRI NIH HHS/ -- U01HG004438/HG/NHGRI NIH HHS/ -- U01HG004446/HG/NHGRI NIH HHS/ -- U01HG004726/HG/NHGRI NIH HHS/ -- U01HG004728/HG/NHGRI NIH HHS/ -- U01HG004729/HG/NHGRI NIH HHS/ -- U01HG004735/HG/NHGRI NIH HHS/ -- U01HG004738/HG/NHGRI NIH HHS/ -- U10 HL054512/HL/NHLBI NIH HHS/ -- U10HL054512/HL/NHLBI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1RR025005/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2011 Sep 11;478(7367):103-9. doi: 10.1038/nature10405.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21909115" target="_blank"〉PubMed〈/a〉

Description: Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Howe, Kerstin -- Clark, Matthew D -- Torroja, Carlos F -- Torrance, James -- Berthelot, Camille -- Muffato, Matthieu -- Collins, John E -- Humphray, Sean -- McLaren, Karen -- Matthews, Lucy -- McLaren, Stuart -- Sealy, Ian -- Caccamo, Mario -- Churcher, Carol -- Scott, Carol -- Barrett, Jeffrey C -- Koch, Romke -- Rauch, Gerd-Jorg -- White, Simon -- Chow, William -- Kilian, Britt -- Quintais, Leonor T -- Guerra-Assuncao, Jose A -- Zhou, Yi -- Gu, Yong -- Yen, Jennifer -- Vogel, Jan-Hinnerk -- Eyre, Tina -- Redmond, Seth -- Banerjee, Ruby -- Chi, Jianxiang -- Fu, Beiyuan -- Langley, Elizabeth -- Maguire, Sean F -- Laird, Gavin K -- Lloyd, David -- Kenyon, Emma -- Donaldson, Sarah -- Sehra, Harminder -- Almeida-King, Jeff -- Loveland, Jane -- Trevanion, Stephen -- Jones, Matt -- Quail, Mike -- Willey, Dave -- Hunt, Adrienne -- Burton, John -- Sims, Sarah -- McLay, Kirsten -- Plumb, Bob -- Davis, Joy -- Clee, Chris -- Oliver, Karen -- Clark, Richard -- Riddle, Clare -- Elliot, David -- Threadgold, Glen -- Harden, Glenn -- Ware, Darren -- Begum, Sharmin -- Mortimore, Beverley -- Kerry, Giselle -- Heath, Paul -- Phillimore, Benjamin -- Tracey, Alan -- Corby, Nicole -- Dunn, Matthew -- Johnson, Christopher -- Wood, Jonathan -- Clark, Susan -- Pelan, Sarah -- Griffiths, Guy -- Smith, Michelle -- Glithero, Rebecca -- Howden, Philip -- Barker, Nicholas -- Lloyd, Christine -- Stevens, Christopher -- Harley, Joanna -- Holt, Karen -- Panagiotidis, Georgios -- Lovell, Jamieson -- Beasley, Helen -- Henderson, Carl -- Gordon, Daria -- Auger, Katherine -- Wright, Deborah -- Collins, Joanna -- Raisen, Claire -- Dyer, Lauren -- Leung, Kenric -- Robertson, Lauren -- Ambridge, Kirsty -- Leongamornlert, Daniel -- McGuire, Sarah -- Gilderthorp, Ruth -- Griffiths, Coline -- Manthravadi, Deepa -- Nichol, Sarah -- Barker, Gary -- Whitehead, Siobhan -- Kay, Michael -- Brown, Jacqueline -- Murnane, Clare -- Gray, Emma -- Humphries, Matthew -- Sycamore, Neil -- Barker, Darren -- Saunders, David -- Wallis, Justene -- Babbage, Anne -- Hammond, Sian -- Mashreghi-Mohammadi, Maryam -- Barr, Lucy -- Martin, Sancha -- Wray, Paul -- Ellington, Andrew -- Matthews, Nicholas -- Ellwood, Matthew -- Woodmansey, Rebecca -- Clark, Graham -- Cooper, James D -- Tromans, Anthony -- Grafham, Darren -- Skuce, Carl -- Pandian, Richard -- Andrews, Robert -- Harrison, Elliot -- Kimberley, Andrew -- Garnett, Jane -- Fosker, Nigel -- Hall, Rebekah -- Garner, Patrick -- Kelly, Daniel -- Bird, Christine -- Palmer, Sophie -- Gehring, Ines -- Berger, Andrea -- Dooley, Christopher M -- Ersan-Urun, Zubeyde -- Eser, Cigdem -- Geiger, Horst -- Geisler, Maria -- Karotki, Lena -- Kirn, Anette -- Konantz, Judith -- Konantz, Martina -- Oberlander, Martina -- Rudolph-Geiger, Silke -- Teucke, Mathias -- Lanz, Christa -- Raddatz, Gunter -- Osoegawa, Kazutoyo -- Zhu, Baoli -- Rapp, Amanda -- Widaa, Sara -- Langford, Cordelia -- Yang, Fengtang -- Schuster, Stephan C -- Carter, Nigel P -- Harrow, Jennifer -- Ning, Zemin -- Herrero, Javier -- Searle, Steve M J -- Enright, Anton -- Geisler, Robert -- Plasterk, Ronald H A -- Lee, Charles -- Westerfield, Monte -- de Jong, Pieter J -- Zon, Leonard I -- Postlethwait, John H -- Nusslein-Volhard, Christiane -- Hubbard, Tim J P -- Roest Crollius, Hugues -- Rogers, Jane -- Stemple, Derek L -- 095908/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- 1 R01 DK55377-01A1/DK/NIDDK NIH HHS/ -- P01 HD022486/HD/NICHD NIH HHS/ -- P01 HD22486/HD/NICHD NIH HHS/ -- R01 GM085318/GM/NIGMS NIH HHS/ -- R01 OD011116/OD/NIH HHS/ -- R01 RR010715/RR/NCRR NIH HHS/ -- R01 RR020833/RR/NCRR NIH HHS/ -- England -- Nature. 2013 Apr 25;496(7446):498-503. doi: 10.1038/nature12111. Epub 2013 Apr 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23594743" target="_blank"〉PubMed〈/a〉

Description: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P 〈 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955183/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955183/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lango Allen, Hana -- Estrada, Karol -- Lettre, Guillaume -- Berndt, Sonja I -- Weedon, Michael N -- Rivadeneira, Fernando -- Willer, Cristen J -- Jackson, Anne U -- Vedantam, Sailaja -- Raychaudhuri, Soumya -- Ferreira, Teresa -- Wood, Andrew R -- Weyant, Robert J -- Segre, Ayellet V -- Speliotes, Elizabeth K -- Wheeler, Eleanor -- Soranzo, Nicole -- Park, Ju-Hyun -- Yang, Jian -- Gudbjartsson, Daniel -- Heard-Costa, Nancy L -- Randall, Joshua C -- Qi, Lu -- Vernon Smith, Albert -- Magi, Reedik -- Pastinen, Tomi -- Liang, Liming -- Heid, Iris M -- Luan, Jian'an -- Thorleifsson, Gudmar -- Winkler, Thomas W -- Goddard, Michael E -- Sin Lo, Ken -- Palmer, Cameron -- Workalemahu, Tsegaselassie -- Aulchenko, Yurii S -- Johansson, Asa -- Zillikens, M Carola -- Feitosa, Mary F -- Esko, Tonu -- Johnson, Toby -- Ketkar, Shamika -- Kraft, Peter -- Mangino, Massimo -- Prokopenko, Inga -- Absher, Devin -- Albrecht, Eva -- Ernst, Florian -- Glazer, Nicole L -- Hayward, Caroline -- Hottenga, Jouke-Jan -- Jacobs, Kevin B -- Knowles, Joshua W -- Kutalik, Zoltan -- Monda, Keri L -- Polasek, Ozren -- Preuss, Michael -- Rayner, Nigel W -- Robertson, Neil R -- Steinthorsdottir, Valgerdur -- Tyrer, Jonathan P -- Voight, Benjamin F -- Wiklund, Fredrik -- Xu, Jianfeng -- Zhao, Jing Hua -- Nyholt, Dale R -- Pellikka, Niina -- Perola, Markus -- Perry, John R B -- Surakka, Ida -- Tammesoo, Mari-Liis -- Altmaier, Elizabeth L -- Amin, Najaf -- Aspelund, Thor -- Bhangale, Tushar -- Boucher, Gabrielle -- Chasman, Daniel I -- Chen, Constance -- Coin, Lachlan -- Cooper, Matthew N -- Dixon, Anna L -- Gibson, Quince -- Grundberg, Elin -- Hao, Ke -- Juhani Junttila, M -- Kaplan, Lee M -- Kettunen, Johannes -- Konig, Inke R -- Kwan, Tony -- Lawrence, Robert W -- Levinson, Douglas F -- Lorentzon, Mattias -- McKnight, Barbara -- Morris, Andrew P -- Muller, Martina -- Suh Ngwa, Julius -- Purcell, Shaun -- Rafelt, Suzanne -- Salem, Rany M -- Salvi, Erika -- Sanna, Serena -- Shi, Jianxin -- Sovio, Ulla -- Thompson, John R -- Turchin, Michael C -- Vandenput, Liesbeth -- Verlaan, Dominique J -- Vitart, Veronique -- White, Charles C -- Ziegler, Andreas -- Almgren, Peter -- Balmforth, Anthony J -- Campbell, Harry -- Citterio, Lorena -- De Grandi, Alessandro -- Dominiczak, Anna -- Duan, Jubao -- Elliott, Paul -- Elosua, Roberto -- Eriksson, Johan G -- Freimer, Nelson B -- Geus, Eco J C -- Glorioso, Nicola -- Haiqing, Shen -- Hartikainen, Anna-Liisa -- Havulinna, Aki S -- Hicks, Andrew A -- Hui, Jennie -- Igl, Wilmar -- Illig, Thomas -- Jula, Antti -- Kajantie, Eero -- Kilpelainen, Tuomas O -- Koiranen, Markku -- Kolcic, Ivana -- Koskinen, Seppo -- Kovacs, Peter -- Laitinen, Jaana -- Liu, Jianjun -- Lokki, Marja-Liisa -- Marusic, Ana -- Maschio, Andrea -- Meitinger, Thomas -- Mulas, Antonella -- Pare, Guillaume -- Parker, Alex N -- Peden, John F -- Petersmann, Astrid -- Pichler, Irene -- Pietilainen, Kirsi H -- Pouta, Anneli -- Ridderstrale, Martin -- Rotter, Jerome I -- Sambrook, Jennifer G -- Sanders, Alan R -- Schmidt, Carsten Oliver -- Sinisalo, Juha -- Smit, Jan H -- Stringham, Heather M -- Bragi Walters, G -- Widen, Elisabeth -- Wild, Sarah H -- Willemsen, Gonneke -- Zagato, Laura -- Zgaga, Lina -- Zitting, Paavo -- Alavere, Helene -- Farrall, Martin -- McArdle, Wendy L -- Nelis, Mari -- Peters, Marjolein J -- Ripatti, Samuli -- van Meurs, Joyce B J -- Aben, Katja K -- Ardlie, Kristin G -- Beckmann, Jacques S -- Beilby, John P -- Bergman, Richard N -- Bergmann, Sven -- Collins, Francis S -- Cusi, Daniele -- den Heijer, Martin -- Eiriksdottir, Gudny -- Gejman, Pablo V -- Hall, Alistair S -- Hamsten, Anders -- Huikuri, Heikki V -- Iribarren, Carlos -- Kahonen, Mika -- Kaprio, Jaakko -- Kathiresan, Sekar -- Kiemeney, Lambertus -- Kocher, Thomas -- Launer, Lenore J -- Lehtimaki, Terho -- Melander, Olle -- Mosley, Tom H Jr -- Musk, Arthur W -- Nieminen, Markku S -- O'Donnell, Christopher J -- Ohlsson, Claes -- Oostra, Ben -- Palmer, Lyle J -- Raitakari, Olli -- Ridker, Paul M -- Rioux, John D -- Rissanen, Aila -- Rivolta, Carlo -- Schunkert, Heribert -- Shuldiner, Alan R -- Siscovick, David S -- Stumvoll, Michael -- Tonjes, Anke -- Tuomilehto, Jaakko -- van Ommen, Gert-Jan -- Viikari, Jorma -- Heath, Andrew C -- Martin, Nicholas G -- Montgomery, Grant W -- Province, Michael A -- Kayser, Manfred -- Arnold, Alice M -- Atwood, Larry D -- Boerwinkle, Eric -- Chanock, Stephen J -- Deloukas, Panos -- Gieger, Christian -- Gronberg, Henrik -- Hall, Per -- Hattersley, Andrew T -- Hengstenberg, Christian -- Hoffman, Wolfgang -- Lathrop, G Mark -- Salomaa, Veikko -- Schreiber, Stefan -- Uda, Manuela -- Waterworth, Dawn -- Wright, Alan F -- Assimes, Themistocles L -- Barroso, Ines -- Hofman, Albert -- Mohlke, Karen L -- Boomsma, Dorret I -- Caulfield, Mark J -- Cupples, L Adrienne -- Erdmann, Jeanette -- Fox, Caroline S -- Gudnason, Vilmundur -- Gyllensten, Ulf -- Harris, Tamara B -- Hayes, Richard B -- Jarvelin, Marjo-Riitta -- Mooser, Vincent -- Munroe, Patricia B -- Ouwehand, Willem H -- Penninx, Brenda W -- Pramstaller, Peter P -- Quertermous, Thomas -- Rudan, Igor -- Samani, Nilesh J -- Spector, Timothy D -- Volzke, Henry -- Watkins, Hugh -- Wilson, James F -- Groop, Leif C -- Haritunians, Talin -- Hu, Frank B -- Kaplan, Robert C -- Metspalu, Andres -- North, Kari E -- Schlessinger, David -- Wareham, Nicholas J -- Hunter, David J -- O'Connell, Jeffrey R -- Strachan, David P -- Wichmann, H-Erich -- Borecki, Ingrid B -- van Duijn, Cornelia M -- Schadt, Eric E -- Thorsteinsdottir, Unnur -- Peltonen, Leena -- Uitterlinden, Andre G -- Visscher, Peter M -- Chatterjee, Nilanjan -- Loos, Ruth J F -- Boehnke, Michael -- McCarthy, Mark I -- Ingelsson, Erik -- Lindgren, Cecilia M -- Abecasis, Goncalo R -- Stefansson, Kari -- Frayling, Timothy M -- Hirschhorn, Joel N -- 064890/Wellcome Trust/United Kingdom -- 068545/Wellcome Trust/United Kingdom -- 068545/Z/02/Wellcome Trust/United Kingdom -- 072856/Wellcome Trust/United Kingdom -- 072960/Wellcome Trust/United Kingdom -- 075491/Wellcome Trust/United Kingdom -- 076113/Wellcome Trust/United Kingdom -- 076113/B/04/Z/Wellcome Trust/United Kingdom -- 076113/C/04/Z/Wellcome Trust/United Kingdom -- 077016/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079557/Wellcome Trust/United Kingdom -- 079771/Wellcome 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GM074518-05/GM/NIGMS NIH HHS/ -- U01 HG004399/HG/NHGRI NIH HHS/ -- U01 HG004399-02/HG/NHGRI NIH HHS/ -- U01 HG004402/HG/NHGRI NIH HHS/ -- U01 HG004402-02/HG/NHGRI NIH HHS/ -- U01 HG005214/HG/NHGRI NIH HHS/ -- U01 HG005214-02/HG/NHGRI NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL069757-10/HL/NHLBI NIH HHS/ -- U01 HL072515/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01 HL080295-04/HL/NHLBI NIH HHS/ -- U01 HL084729/HL/NHLBI NIH HHS/ -- U01 HL084729-03/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 HL084756-03/HL/NHLBI NIH HHS/ -- U01 MH079469/MH/NIMH NIH HHS/ -- U01 MH079469-03/MH/NIMH NIH HHS/ -- U01 MH079470/MH/NIMH NIH HHS/ -- U01 MH079470-03/MH/NIMH NIH HHS/ -- U01-CA098233/CA/NCI NIH HHS/ -- U01-GM074518/GM/NIGMS NIH HHS/ -- U01-HG004399/HG/NHGRI NIH HHS/ -- U01-HG004402/HG/NHGRI NIH HHS/ -- U01-HL080295/HL/NHLBI NIH HHS/ -- U01-HL084756/HL/NHLBI NIH HHS/ -- U01-HL72515/HL/NHLBI NIH HHS/ -- U01-MH79469/MH/NIMH NIH HHS/ -- U01-MH79470/MH/NIMH NIH HHS/ -- U54-RR020278/RR/NCRR NIH HHS/ -- UL1-RR025005/RR/NCRR NIH HHS/ -- Z01-AG00675/AG/NIA NIH HHS/ -- Z01-AG007380/AG/NIA NIH HHS/ -- Z01-HG000024/HG/NHGRI NIH HHS/ -- Cancer Research UK/United Kingdom -- Intramural NIH HHS/ -- England -- Nature. 2010 Oct 14;467(7317):832-8. doi: 10.1038/nature09410. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881960" target="_blank"〉PubMed〈/a〉

Description: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Multiple Sclerosis Genetics Consortium -- Wellcome Trust Case Control Consortium 2 -- Sawcer, Stephen -- Hellenthal, Garrett -- Pirinen, Matti -- Spencer, Chris C A -- Patsopoulos, Nikolaos A -- Moutsianas, Loukas -- Dilthey, Alexander -- Su, Zhan -- Freeman, Colin -- Hunt, Sarah E -- Edkins, Sarah -- Gray, Emma -- Booth, David R -- Potter, Simon C -- Goris, An -- Band, Gavin -- Oturai, Annette Bang -- Strange, Amy -- Saarela, Janna -- Bellenguez, Celine -- Fontaine, Bertrand -- Gillman, Matthew -- Hemmer, Bernhard -- Gwilliam, Rhian -- Zipp, Frauke -- Jayakumar, Alagurevathi -- Martin, Roland -- Leslie, Stephen -- Hawkins, Stanley -- Giannoulatou, Eleni -- D'alfonso, Sandra -- Blackburn, Hannah -- Martinelli Boneschi, Filippo -- Liddle, Jennifer -- Harbo, Hanne F -- Perez, Marc L -- Spurkland, Anne -- Waller, Matthew J -- Mycko, Marcin P -- Ricketts, Michelle -- Comabella, Manuel -- Hammond, Naomi -- Kockum, Ingrid -- McCann, Owen T -- Ban, Maria -- Whittaker, Pamela -- Kemppinen, Anu -- Weston, Paul -- Hawkins, Clive -- Widaa, Sara -- Zajicek, John -- Dronov, Serge -- Robertson, Neil -- Bumpstead, Suzannah J -- Barcellos, Lisa F -- Ravindrarajah, Rathi -- Abraham, Roby -- Alfredsson, Lars -- Ardlie, Kristin -- Aubin, Cristin -- Baker, Amie -- Baker, Katharine -- Baranzini, Sergio E -- Bergamaschi, Laura -- Bergamaschi, Roberto -- Bernstein, Allan -- Berthele, Achim -- Boggild, Mike -- Bradfield, Jonathan P -- Brassat, David -- Broadley, Simon A -- Buck, Dorothea -- Butzkueven, Helmut -- Capra, Ruggero -- Carroll, William M -- Cavalla, Paola -- Celius, Elisabeth G -- Cepok, Sabine -- Chiavacci, Rosetta -- Clerget-Darpoux, Francoise -- Clysters, Katleen -- Comi, Giancarlo -- Cossburn, Mark -- Cournu-Rebeix, Isabelle -- Cox, Mathew B -- Cozen, Wendy -- Cree, Bruce A C -- Cross, Anne H -- Cusi, Daniele -- Daly, Mark J -- Davis, Emma -- de Bakker, Paul I W -- Debouverie, Marc -- D'hooghe, Marie Beatrice -- Dixon, Katherine -- Dobosi, Rita -- Dubois, Benedicte -- Ellinghaus, David -- Elovaara, Irina -- Esposito, Federica -- Fontenille, Claire -- Foote, Simon -- Franke, Andre -- Galimberti, Daniela -- Ghezzi, Angelo -- Glessner, Joseph -- Gomez, Refujia -- Gout, Olivier -- Graham, Colin -- Grant, Struan F A -- Guerini, Franca Rosa -- Hakonarson, Hakon -- Hall, Per -- Hamsten, Anders -- Hartung, Hans-Peter -- Heard, Rob N -- Heath, Simon -- Hobart, Jeremy -- Hoshi, Muna -- Infante-Duarte, Carmen -- Ingram, Gillian -- Ingram, Wendy -- Islam, Talat -- Jagodic, Maja -- Kabesch, Michael -- Kermode, Allan G -- Kilpatrick, Trevor J -- Kim, Cecilia -- Klopp, Norman -- Koivisto, Keijo -- Larsson, Malin -- Lathrop, Mark -- Lechner-Scott, Jeannette S -- Leone, Maurizio A -- Leppa, Virpi -- Liljedahl, Ulrika -- Bomfim, Izaura Lima -- Lincoln, Robin R -- Link, Jenny -- Liu, Jianjun -- Lorentzen, Aslaug R -- Lupoli, Sara -- Macciardi, Fabio -- Mack, Thomas -- Marriott, Mark -- Martinelli, Vittorio -- Mason, Deborah -- McCauley, Jacob L -- Mentch, Frank -- Mero, Inger-Lise -- Mihalova, Tania -- Montalban, Xavier -- Mottershead, John -- Myhr, Kjell-Morten -- Naldi, Paola -- Ollier, William -- Page, Alison -- Palotie, Aarno -- Pelletier, Jean -- Piccio, Laura -- Pickersgill, Trevor -- Piehl, Fredrik -- Pobywajlo, Susan -- Quach, Hong L -- Ramsay, Patricia P -- Reunanen, Mauri -- Reynolds, Richard -- Rioux, John D -- Rodegher, Mariaemma -- Roesner, Sabine -- Rubio, Justin P -- Ruckert, Ina-Maria -- Salvetti, Marco -- Salvi, Erika -- Santaniello, Adam -- Schaefer, Catherine A -- Schreiber, Stefan -- Schulze, Christian -- Scott, Rodney J -- Sellebjerg, Finn -- Selmaj, Krzysztof W -- Sexton, David -- Shen, Ling -- Simms-Acuna, Brigid -- Skidmore, Sheila -- Sleiman, Patrick M A -- Smestad, Cathrine -- Sorensen, Per Soelberg -- Sondergaard, Helle Bach -- Stankovich, Jim -- Strange, Richard C -- Sulonen, Anna-Maija -- Sundqvist, Emilie -- Syvanen, Ann-Christine -- Taddeo, Francesca -- Taylor, Bruce -- Blackwell, Jenefer M -- Tienari, Pentti -- Bramon, Elvira -- Tourbah, Ayman -- Brown, Matthew A -- Tronczynska, Ewa -- Casas, Juan P -- Tubridy, Niall -- Corvin, Aiden -- Vickery, Jane -- Jankowski, Janusz -- Villoslada, Pablo -- Markus, Hugh S -- Wang, Kai -- Mathew, Christopher G -- Wason, James -- Palmer, Colin N A -- Wichmann, H-Erich -- Plomin, Robert -- Willoughby, Ernest -- Rautanen, Anna -- Winkelmann, Juliane -- Wittig, Michael -- Trembath, Richard C -- Yaouanq, Jacqueline -- Viswanathan, Ananth C -- Zhang, Haitao -- Wood, Nicholas W -- Zuvich, Rebecca -- Deloukas, Panos -- Langford, Cordelia -- Duncanson, Audrey -- Oksenberg, Jorge R -- Pericak-Vance, Margaret A -- Haines, Jonathan L -- Olsson, Tomas -- Hillert, Jan -- Ivinson, Adrian J -- De Jager, Philip L -- Peltonen, Leena -- Stewart, Graeme J -- Hafler, David A -- Hauser, Stephen L -- McVean, Gil -- Donnelly, Peter -- Compston, Alastair -- 068545/Z/02/Wellcome Trust/United Kingdom -- 075491/Z/04/Z/Wellcome Trust/United Kingdom -- 084702/Wellcome Trust/United Kingdom -- 085475/Wellcome Trust/United Kingdom -- 085475/B/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 898/Multiple Sclerosis Society/United Kingdom -- AI076544/AI/NIAID NIH HHS/ -- CA104021/CA/NCI NIH HHS/ -- G0100594/Medical Research Council/United Kingdom -- G0400017/Medical Research Council/United Kingdom -- G0700061/Medical Research Council/United Kingdom -- G0901310/Medical Research Council/United Kingdom -- G0901461/Medical Research Council/United Kingdom -- G19/2/Medical Research Council/United Kingdom -- K23N/S048869/PHS HHS/ -- NS032830/NS/NINDS NIH HHS/ -- NS049477/NS/NINDS NIH HHS/ -- NS049510/NS/NINDS NIH HHS/ -- NS067305/NS/NINDS NIH HHS/ -- NS19142/NS/NINDS NIH HHS/ -- NS26799/NS/NINDS NIH HHS/ -- NS43559/NS/NINDS NIH HHS/ -- PDA/02/06/016/Department of Health/United Kingdom -- R01 NS026799/NS/NINDS NIH HHS/ -- R01 NS049477/NS/NINDS NIH HHS/ -- R01 NS049477-06A1/NS/NINDS NIH HHS/ -- RR020092/RR/NCRR NIH HHS/ -- RR024992/RR/NCRR NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Aug 10;476(7359):214-9. doi: 10.1038/nature10251.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21833088" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138491/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138491/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉H3Africa Consortium -- Rotimi, Charles -- Abayomi, Akin -- Abimiku, Alash'le -- Adabayeri, Victoria May -- Adebamowo, Clement -- Adebiyi, Ezekiel -- Ademola, Adebowale D -- Adeyemo, Adebowale -- Adu, Dwomoa -- Affolabi, Dissou -- Agongo, Godfred -- Ajayi, Samuel -- Akarolo-Anthony, Sally -- Akinyemi, Rufus -- Akpalu, Albert -- Alberts, Marianne -- Alonso Betancourt, Orlando -- Alzohairy, Ahmed Mansour -- Ameni, Gobena -- Amodu, Olukemi -- Anabwani, Gabriel -- Andersen, Kristian -- Arogundade, Fatiu -- Arulogun, Oyedunni -- Asogun, Danny -- Bakare, Rasheed -- Balde, Naby -- Baniecki, Mary Lynn -- Beiswanger, Christine -- Benkahla, Alia -- Bethke, Lara -- Boehnke, Micheal -- Boima, Vincent -- Brandful, James -- Brooks, Andrew I -- Brosius, Frank C -- Brown, Chester -- Bucheton, Bruno -- Burke, David T -- Burnett, Barrington G -- Carrington-Lawrence, Stacy -- Carstens, Nadia -- Chisi, John -- Christoffels, Alan -- Cooper, Richard -- Cordell, Heather -- Crowther, Nigel -- Croxton, Talishiea -- de Vries, Jantina -- Derr, Leslie -- Donkor, Peter -- Doumbia, Seydou -- Duncanson, Audrey -- Ekem, Ivy -- El Sayed, Ahmed -- Engel, Mark E -- Enyaru, John C K -- Everett, Dean -- Fadlelmola, Faisal M -- Fakunle, Eyitayo -- Fischbeck, Kenneth H -- Fischer, Anne -- Folarin, Onikepe -- Gamieldien, Junaid -- Garry, Robert F -- Gaseitsiwe, Simani -- Gbadegesin, Rasheed -- Ghansah, Anita -- Giovanni, Maria -- Goesbeck, Parham -- Gomez-Olive, F Xavier -- Grant, Donald S -- Grewal, Ravnit -- Guyer, Mark -- Hanchard, Neil A -- Happi, Christian T -- Hazelhurst, Scott -- Hennig, Branwen J -- Hertz-, Christiane -- Fowler -- Hide, Winston -- Hilderbrandt, Friedhelm -- Hugo-Hamman, Christopher -- Ibrahim, Muntaser E -- James, Regina -- Jaufeerally-Fakim, Yasmina -- Jenkins, Carolyn -- Jentsch, Ute -- Jiang, Pan-Pan -- Joloba, Moses -- Jongeneel, Victor -- Joubert, Fourie -- Kader, Mukthar -- Kahn, Kathleen -- Kaleebu, Pontiano -- Kapiga, Saidi H -- Kassim, Samar Kamal -- Kasvosve, Ishmael -- Kayondo, Jonathan -- Keavney, Bernard -- Kekitiinwa, Adeodata -- Khan, Sheik Humarr -- Kimmel, Paul -- King, Mary-Claire -- Kleta, Robert -- Koffi, Mathurin -- Kopp, Jeffrey -- Kretzler, Matthias -- Kumuthini, Judit -- Kyobe, Samuel -- Kyobutungi, Catherine -- Lackland, Daniel T -- Lacourciere, Karen A -- Landoure, Guida -- Lawlor, Rita -- Lehner, Thomas -- Lesosky, Maia -- Levitt, Naomi -- Littler, Katherine -- Lombard, Zane -- Loring, Jeanne F -- Lyantagaye, Sylvester -- Macleod, Annette -- Madden, Ebony B -- Mahomva, Chengetai R -- Makani, Julie -- Mamven, Manmak -- Marape, Marape -- Mardon, Graeme -- Marshall, Patricia -- Martin, Darren P -- Masiga, Daniel -- Mason, Robin -- Mate-Kole, Michael -- Matovu, Enock -- Mayige, Mary -- Mayosi, Bongani M -- Mbanya, Jean Claude -- McCurdy, Sheryl A -- McCarthy, Mark I -- McIlleron, Helen -- Mc'Ligeyo, S O -- Merle, Corrine -- Mocumbi, Ana Olga -- Mondo, Charles -- Moran, John V -- Motala, Ayesha -- Moxey-Mims, Marva -- Mpoloka, Wata Sununguko -- Msefula, Chisomo L -- Mthiyane, Thuli -- Mulder, Nicola -- Mulugeta, Gebregziab her -- Mumba, Dieuodonne -- Musuku, John -- Nagdee, Mo -- Nash, Oyekanmi -- Ndiaye, Daouda -- Nguyen, Anh Quynh -- Nicol, Mark -- Nkomazana, Oathokwa -- Norris, Shane -- Nsangi, Betty -- Nyarko, Alexander -- Nyirenda, Moffat -- Obe, Eileen -- Obiakor, Reginald -- Oduro, Abraham -- Ofori-Acquah, Solomon F -- Ogah, Okechukwu -- Ogendo, Stephen -- Ohene-Frempong, Kwaku -- Ojo, Akinlolu -- Olanrewaju, Timothy -- Oli, John -- Osafo, Charlotte -- Ouwe Missi Oukem-Boyer, Odile -- Ovbiagele, Bruce -- Owen, Andrew -- Owolabi, Mayowa Ojo -- Owolabi, Lukman -- Owusu-Dabo, Ellis -- Pare, Guillaume -- Parekh, Rulan -- Patterton, Hugh G -- Penno, Margaret B -- Peterson, Jane -- Pieper, Rembert -- Plange-Rhule, Jacob -- Pollak, Martin -- Puzak, Julia -- Ramesar, Rajkumar S -- Ramsay, Michele -- Rasooly, Rebekah -- Reddy, Shiksha -- Sabeti, Pardis C -- Sagoe, Kwamena -- Salako, Tunde -- Samassekou, Oumar -- Sandhu, Manjinder S -- Sankoh, Osman -- Sarfo, Fred Stephen -- Sarr, Marie -- Shaboodien, Gasnat -- Sidibe, Issa -- Simo, Gustave -- Simuunza, Martin -- Smeeth, Liam -- Sobngwi, Eugene -- Soodyall, Himla -- Sorgho, Hermann -- Sow Bah, Oumou -- Srinivasan, Sudha -- Stein, Dan J -- Susser, Ezra S -- Swanepoel, Carmen -- Tangwa, Godfred -- Tareila, Andrew -- Tastan Bishop, Ozlem -- Tayo, Bamidele -- Tiffin, Nicki -- Tinto, Halidou -- Tobin, Ekaete -- Tollman, Stephen Meir -- Traore, Mahamadou -- Treadwell, Marsha J -- Troyer, Jennifer -- Tsimako-Johnstone, Masego -- Tukei, Vincent -- Ulasi, Ifeoma -- Ulenga, Nzovu -- van Rooyen, Beverley -- Wachinou, Ablo Prudence -- Waddy, Salina P -- Wade, Alisha -- Wayengera, Misaki -- Whitworth, James -- Wideroff, Louise -- Winkler, Cheryl A -- Winnicki, Sarah -- Wonkam, Ambroise -- Yewondwos, Mengistu -- sen, Tadase -- Yozwiak, Nathan -- Zar, Heather -- 085349/Wellcome Trust/United Kingdom -- 095009/Wellcome Trust/United Kingdom -- 095201/Wellcome Trust/United Kingdom -- 098504/Wellcome Trust/United Kingdom -- 104111/Wellcome Trust/United Kingdom -- MC_U123292700/Medical Research Council/United Kingdom -- P20 MD006899/MD/NIMHD NIH HHS/ -- R01 AI104621/AI/NIAID NIH HHS/ -- RG/08/012/25941/British Heart Foundation/United Kingdom -- U01 HG007044/HG/NHGRI NIH HHS/ -- U41 HG006941/HG/NHGRI NIH HHS/ -- U54 AI110398/AI/NIAID NIH HHS/ -- U54 HG006938/HG/NHGRI NIH HHS/ -- U54 HG006939/HG/NHGRI NIH HHS/ -- U54 HG007479/HG/NHGRI NIH HHS/ -- UH2 HG007051/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2014 Jun 20;344(6190):1346-8. doi: 10.1126/science.1251546.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24948725" target="_blank"〉PubMed〈/a〉

Description: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in 〉100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P 〈 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039276/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039276/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Teslovich, Tanya M -- Musunuru, Kiran -- Smith, Albert V -- Edmondson, Andrew C -- Stylianou, Ioannis M -- Koseki, Masahiro -- Pirruccello, James P -- Ripatti, Samuli -- Chasman, Daniel I -- Willer, Cristen J -- Johansen, Christopher T -- Fouchier, Sigrid W -- Isaacs, Aaron -- Peloso, Gina M -- Barbalic, Maja -- Ricketts, Sally L -- Bis, Joshua C -- Aulchenko, Yurii S -- Thorleifsson, Gudmar -- Feitosa, Mary F -- Chambers, John -- Orho-Melander, Marju -- Melander, Olle -- Johnson, Toby -- Li, Xiaohui -- Guo, Xiuqing -- Li, Mingyao -- Shin Cho, Yoon -- Jin Go, Min -- Jin Kim, Young -- Lee, Jong-Young -- Park, Taesung -- Kim, Kyunga -- Sim, Xueling -- Twee-Hee Ong, Rick -- Croteau-Chonka, Damien C -- Lange, Leslie A -- Smith, Joshua D -- Song, Kijoung -- Hua Zhao, Jing -- Yuan, Xin -- Luan, Jian'an -- Lamina, Claudia -- Ziegler, Andreas -- Zhang, Weihua -- Zee, Robert Y L -- Wright, Alan F -- Witteman, Jacqueline C M -- Wilson, James F -- Willemsen, Gonneke -- Wichmann, H-Erich -- Whitfield, John B -- Waterworth, Dawn M -- Wareham, Nicholas J -- Waeber, Gerard -- Vollenweider, Peter -- Voight, Benjamin F -- Vitart, Veronique -- Uitterlinden, Andre G -- Uda, Manuela -- Tuomilehto, Jaakko -- Thompson, John R -- Tanaka, Toshiko -- Surakka, Ida -- Stringham, Heather M -- Spector, Tim D -- Soranzo, Nicole -- Smit, Johannes H -- Sinisalo, Juha -- Silander, Kaisa -- Sijbrands, Eric J G -- Scuteri, Angelo -- Scott, James -- Schlessinger, David -- Sanna, Serena -- Salomaa, Veikko -- Saharinen, Juha -- Sabatti, Chiara -- Ruokonen, Aimo -- Rudan, Igor -- Rose, Lynda M -- Roberts, Robert -- Rieder, Mark -- Psaty, Bruce M -- Pramstaller, Peter P -- Pichler, Irene -- Perola, Markus -- Penninx, Brenda W J H -- Pedersen, Nancy L -- Pattaro, Cristian -- Parker, Alex N -- Pare, Guillaume -- Oostra, Ben A -- O'Donnell, Christopher J -- Nieminen, Markku S -- Nickerson, Deborah A -- Montgomery, Grant W -- Meitinger, Thomas -- McPherson, Ruth -- McCarthy, Mark I -- McArdle, Wendy -- Masson, David -- Martin, Nicholas G -- Marroni, Fabio -- Mangino, Massimo -- Magnusson, Patrik K E -- Lucas, Gavin -- Luben, Robert -- Loos, Ruth J F -- Lokki, Marja-Liisa -- Lettre, Guillaume -- Langenberg, Claudia -- Launer, Lenore J -- Lakatta, Edward G -- Laaksonen, Reijo -- Kyvik, Kirsten O -- Kronenberg, Florian -- Konig, Inke R -- Khaw, Kay-Tee -- Kaprio, Jaakko -- Kaplan, Lee M -- Johansson, Asa -- Jarvelin, Marjo-Riitta -- Janssens, A Cecile J W -- Ingelsson, Erik -- Igl, Wilmar -- Kees Hovingh, G -- Hottenga, Jouke-Jan -- Hofman, Albert -- Hicks, Andrew A -- Hengstenberg, Christian -- Heid, Iris M -- Hayward, Caroline -- Havulinna, Aki S -- Hastie, Nicholas D -- Harris, Tamara B -- Haritunians, Talin -- Hall, Alistair S -- Gyllensten, Ulf -- Guiducci, Candace -- Groop, Leif C -- Gonzalez, Elena -- Gieger, Christian -- Freimer, Nelson B -- Ferrucci, Luigi -- Erdmann, Jeanette -- Elliott, Paul -- Ejebe, Kenechi G -- Doring, Angela -- Dominiczak, Anna F -- Demissie, Serkalem -- Deloukas, Panagiotis -- de Geus, Eco J C -- de Faire, Ulf -- Crawford, Gabriel -- Collins, Francis S -- Chen, Yii-der I -- Caulfield, Mark J -- Campbell, Harry -- Burtt, Noel P -- Bonnycastle, Lori L -- Boomsma, Dorret I -- Boekholdt, S Matthijs -- Bergman, Richard N -- Barroso, Ines -- Bandinelli, Stefania -- Ballantyne, Christie M -- Assimes, Themistocles L -- Quertermous, Thomas -- Altshuler, David -- Seielstad, Mark -- Wong, Tien Y -- Tai, E-Shyong -- Feranil, Alan B -- Kuzawa, Christopher W -- Adair, Linda S -- Taylor, Herman A Jr -- Borecki, Ingrid B -- Gabriel, Stacey B -- Wilson, James G -- Holm, Hilma -- Thorsteinsdottir, Unnur -- Gudnason, Vilmundur -- Krauss, Ronald M -- Mohlke, Karen L -- Ordovas, Jose M -- Munroe, Patricia B -- Kooner, Jaspal S -- Tall, Alan R -- Hegele, Robert A -- Kastelein, John J P -- Schadt, Eric E -- Rotter, Jerome I -- Boerwinkle, Eric -- Strachan, David P -- Mooser, Vincent -- Stefansson, Kari -- Reilly, Muredach P -- Samani, Nilesh J -- Schunkert, Heribert -- Cupples, L Adrienne -- Sandhu, Manjinder S -- Ridker, Paul M -- Rader, Daniel J -- van Duijn, Cornelia M -- Peltonen, Leena -- Abecasis, Goncalo R -- Boehnke, Michael -- Kathiresan, Sekar -- 068545/Z/02/Wellcome Trust/United Kingdom -- 076113/B/04/Z/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 1Z01 HG000024/HG/NHGRI NIH HHS/ -- 5R01DK06833603/DK/NIDDK NIH HHS/ -- 5R01DK07568102/DK/NIDDK NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01HL08770003/HL/NHLBI NIH HHS/ -- 5R01HL08821502/HL/NHLBI NIH HHS/ -- CA 047988/CA/NCI NIH HHS/ -- CZB/4/710/Chief Scientist Office/United Kingdom -- DK062370/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK072193/DK/NIDDK NIH HHS/ -- DK078150/DK/NIDDK NIH HHS/ -- DK56350/DK/NIDDK NIH HHS/ -- ES10126/ES/NIEHS NIH HHS/ -- G0000934/Medical Research Council/United Kingdom -- G0401527/Medical Research Council/United Kingdom -- G0601966/Medical Research Council/United Kingdom -- G0700931/Medical Research Council/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G0801566/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- G9521010D/Medical Research Council/United Kingdom -- HHSN268200625226C/PHS HHS/ -- HL 04381/HL/NHLBI NIH HHS/ -- HL 080467/HL/NHLBI NIH HHS/ -- HL-54776/HL/NHLBI NIH HHS/ -- HL085144/HL/NHLBI NIH HHS/ -- K99 HL098364/HL/NHLBI NIH HHS/ -- K99 HL098364-01/HL/NHLBI NIH HHS/ -- K99HL094535/HL/NHLBI NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- MC_QA137934/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- MC_U127561128/Medical Research Council/United Kingdom -- N01 HC-15103/HC/NHLBI NIH HHS/ -- N01 HC-55222/HC/NHLBI NIH HHS/ -- N01-AG-12100/AG/NIA NIH HHS/ -- N01-HC-25195/HC/NHLBI NIH HHS/ -- N01-HC-35129/HC/NHLBI NIH HHS/ -- N01-HC-45133/HC/NHLBI NIH HHS/ -- N01-HC-55015/HC/NHLBI NIH HHS/ -- N01-HC-55016/HC/NHLBI NIH HHS/ -- N01-HC-55018/HC/NHLBI NIH HHS/ -- N01-HC-55019/HC/NHLBI NIH HHS/ -- N01-HC-55020/HC/NHLBI NIH HHS/ -- N01-HC-55021/HC/NHLBI NIH HHS/ -- N01-HC-55022/HC/NHLBI NIH HHS/ -- N01-HC-75150/HC/NHLBI NIH HHS/ -- N01-HC-85079/HC/NHLBI NIH HHS/ -- N01-HC-85080/HC/NHLBI NIH HHS/ -- N01-HC-85081/HC/NHLBI NIH HHS/ -- N01-HC-85082/HC/NHLBI NIH HHS/ -- N01-HC-85083/HC/NHLBI NIH HHS/ -- N01-HC-85084/HC/NHLBI NIH HHS/ -- N01-HC-85085/HC/NHLBI NIH HHS/ -- N01-HC-85086/HC/NHLBI NIH HHS/ -- N01-HG-65403/HG/NHGRI NIH HHS/ -- N02-HL-6-4278/HL/NHLBI NIH HHS/ -- PG/02/128/British Heart Foundation/United Kingdom -- PG/08/094/British Heart Foundation/United Kingdom -- PG/08/094/26019/British Heart Foundation/United Kingdom -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK078150/DK/NIDDK NIH HHS/ -- R01 HL087647/HL/NHLBI NIH HHS/ -- R01 HL087676/HL/NHLBI NIH HHS/ -- R01 HL089650/HL/NHLBI NIH HHS/ -- R01HL086694/HL/NHLBI NIH HHS/ -- R01HL087641/HL/NHLBI NIH HHS/ -- R01HL087652/HL/NHLBI NIH HHS/ -- R01HL59367/HL/NHLBI NIH HHS/ -- R24 HD050924/HD/NICHD NIH HHS/ -- RC1 HL099634/HL/NHLBI NIH HHS/ -- RC1 HL099634-02/HL/NHLBI NIH HHS/ -- RC1 HL099793/HL/NHLBI NIH HHS/ -- RC2 HL101864,/HL/NHLBI NIH HHS/ -- RC2 HL102419/HL/NHLBI NIH HHS/ -- RG/07/005/23633/British Heart Foundation/United Kingdom -- RR20649/RR/NCRR NIH HHS/ -- SP/08/005/25115/British Heart Foundation/United Kingdom -- T32 GM007092/GM/NIGMS NIH HHS/ -- T32 HG00040/HG/NHGRI NIH HHS/ -- T32HL007208/HL/NHLBI NIH HHS/ -- TW05596/TW/FIC NIH HHS/ -- U01 DK062370/DK/NIDDK NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01HG004402/HG/NHGRI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1RR025005/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):707-13. doi: 10.1038/nature09270.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686565" target="_blank"〉PubMed〈/a〉

Description: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892339/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892339/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wellcome Trust Case Control Consortium -- Craddock, Nick -- Hurles, Matthew E -- Cardin, Niall -- Pearson, Richard D -- Plagnol, Vincent -- Robson, Samuel -- Vukcevic, Damjan -- Barnes, Chris -- Conrad, Donald F -- Giannoulatou, Eleni -- Holmes, Chris -- Marchini, Jonathan L -- Stirrups, Kathy -- Tobin, Martin D -- Wain, Louise V -- Yau, Chris -- Aerts, Jan -- Ahmad, Tariq -- Andrews, T Daniel -- Arbury, Hazel -- Attwood, Anthony -- Auton, Adam -- Ball, Stephen G -- Balmforth, Anthony J -- Barrett, Jeffrey C -- Barroso, Ines -- Barton, Anne -- Bennett, Amanda J -- Bhaskar, Sanjeev -- Blaszczyk, Katarzyna -- Bowes, John -- Brand, Oliver J -- Braund, Peter S -- Bredin, Francesca -- Breen, Gerome -- Brown, Morris J -- Bruce, Ian N -- Bull, Jaswinder -- Burren, Oliver S -- Burton, John -- Byrnes, Jake -- Caesar, Sian -- Clee, Chris M -- Coffey, Alison J -- Connell, John M C -- Cooper, Jason D -- Dominiczak, Anna F -- Downes, Kate -- Drummond, Hazel E -- Dudakia, Darshna -- Dunham, Andrew -- Ebbs, Bernadette -- Eccles, Diana -- Edkins, Sarah -- Edwards, Cathryn -- Elliot, Anna -- Emery, Paul -- Evans, David M -- Evans, Gareth -- Eyre, Steve -- Farmer, Anne -- Ferrier, I Nicol -- Feuk, Lars -- Fitzgerald, Tomas -- Flynn, Edward -- Forbes, Alistair -- Forty, Liz -- Franklyn, Jayne A -- Freathy, Rachel M -- Gibbs, Polly -- Gilbert, Paul -- Gokumen, Omer -- Gordon-Smith, Katherine -- Gray, Emma -- Green, Elaine -- Groves, Chris J -- Grozeva, Detelina -- Gwilliam, Rhian -- Hall, Anita -- Hammond, Naomi -- Hardy, Matt -- Harrison, Pile -- Hassanali, Neelam -- Hebaishi, Husam -- Hines, Sarah -- Hinks, Anne -- Hitman, Graham A -- Hocking, Lynne -- Howard, Eleanor -- Howard, Philip -- Howson, Joanna M M -- Hughes, Debbie -- Hunt, Sarah -- Isaacs, John D -- Jain, Mahim -- Jewell, Derek P -- Johnson, Toby -- Jolley, Jennifer D -- Jones, Ian R -- Jones, Lisa A -- Kirov, George -- Langford, Cordelia F -- Lango-Allen, Hana -- Lathrop, G Mark -- Lee, James -- Lee, Kate L -- Lees, Charlie -- Lewis, Kevin -- Lindgren, Cecilia M -- Maisuria-Armer, Meeta -- Maller, Julian -- Mansfield, John -- Martin, Paul -- Massey, Dunecan C O -- McArdle, Wendy L -- McGuffin, Peter -- McLay, Kirsten E -- Mentzer, Alex -- Mimmack, Michael L -- Morgan, Ann E -- Morris, Andrew P -- Mowat, Craig -- Myers, Simon -- Newman, William -- Nimmo, Elaine R -- O'Donovan, Michael C -- Onipinla, Abiodun -- Onyiah, Ifejinelo -- Ovington, Nigel R -- Owen, Michael J -- Palin, Kimmo -- Parnell, Kirstie -- Pernet, David -- Perry, John R B -- Phillips, Anne -- Pinto, Dalila -- Prescott, Natalie J -- Prokopenko, Inga -- Quail, Michael A -- Rafelt, Suzanne -- Rayner, Nigel W -- Redon, Richard -- Reid, David M -- Renwick -- Ring, Susan M -- Robertson, Neil -- Russell, Ellie -- St Clair, David -- Sambrook, Jennifer G -- Sanderson, Jeremy D -- Schuilenburg, Helen -- Scott, Carol E -- Scott, Richard -- Seal, Sheila -- Shaw-Hawkins, Sue -- Shields, Beverley M -- Simmonds, Matthew J -- Smyth, Debbie J -- Somaskantharajah, Elilan -- Spanova, Katarina -- Steer, Sophia -- Stephens, Jonathan -- Stevens, Helen E -- Stone, Millicent A -- Su, Zhan -- Symmons, Deborah P M -- Thompson, John R -- Thomson, Wendy -- Travers, Mary E -- Turnbull, Clare -- Valsesia, Armand -- Walker, Mark -- Walker, Neil M -- Wallace, Chris -- Warren-Perry, Margaret -- Watkins, Nicholas A -- Webster, John -- Weedon, Michael N -- Wilson, Anthony G -- Woodburn, Matthew -- Wordsworth, B Paul -- Young, Allan H -- Zeggini, Eleftheria -- Carter, Nigel P -- Frayling, Timothy M -- Lee, Charles -- McVean, Gil -- Munroe, Patricia B -- Palotie, Aarno -- Sawcer, Stephen J -- Scherer, Stephen W -- Strachan, David P -- Tyler-Smith, Chris -- Brown, Matthew A -- Burton, Paul R -- Caulfield, Mark J -- Compston, Alastair -- Farrall, Martin -- Gough, Stephen C L -- Hall, Alistair S -- Hattersley, Andrew T -- Hill, Adrian V S -- Mathew, Christopher G -- Pembrey, Marcus -- Satsangi, Jack -- Stratton, Michael R -- Worthington, Jane -- Deloukas, Panos -- Duncanson, Audrey -- Kwiatkowski, Dominic P -- McCarthy, Mark I -- Ouwehand, Willem -- Parkes, Miles -- Rahman, Nazneen -- Todd, John A -- Samani, Nilesh J -- Donnelly, Peter -- 061858/Wellcome Trust/United Kingdom -- 083948/Wellcome Trust/United Kingdom -- 089989/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 17552/Arthritis Research UK/United Kingdom -- CZB/4/540/Chief Scientist Office/United Kingdom -- ETM/137/Chief Scientist Office/United Kingdom -- ETM/75/Chief Scientist Office/United Kingdom -- G0000934/Medical Research Council/United Kingdom -- G0400874/Medical Research Council/United Kingdom -- G0500115/Medical Research Council/United Kingdom -- G0501942/Medical Research Council/United Kingdom -- G0600329/Medical Research Council/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- G0700491/Medical Research Council/United Kingdom -- G0701003/Medical Research Council/United Kingdom -- G0701420/Medical Research Council/United Kingdom -- G0701810/Medical Research Council/United Kingdom -- G0701810(85517)/Medical Research Council/United Kingdom -- G0800383/Medical Research Council/United Kingdom -- G0800509/Medical Research Council/United Kingdom -- G0800759/Medical Research Council/United Kingdom -- G19/9/Medical Research Council/United Kingdom -- G90/106/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- MC_UP_A390_1107/Medical Research Council/United Kingdom -- RG/09/012/28096/British Heart Foundation/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Apr 1;464(7289):713-20. doi: 10.1038/nature08979.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360734" target="_blank"〉PubMed〈/a〉

Description: The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (〈1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021798/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021798/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pinto, Dalila -- Pagnamenta, Alistair T -- Klei, Lambertus -- Anney, Richard -- Merico, Daniele -- Regan, Regina -- Conroy, Judith -- Magalhaes, Tiago R -- Correia, Catarina -- Abrahams, Brett S -- Almeida, Joana -- Bacchelli, Elena -- Bader, Gary D -- Bailey, Anthony J -- Baird, Gillian -- Battaglia, Agatino -- Berney, Tom -- Bolshakova, Nadia -- Bolte, Sven -- Bolton, Patrick F -- Bourgeron, Thomas -- Brennan, Sean -- Brian, Jessica -- Bryson, Susan E -- Carson, Andrew R -- Casallo, Guillermo -- Casey, Jillian -- Chung, Brian H Y -- Cochrane, Lynne -- Corsello, Christina -- Crawford, Emily L -- Crossett, Andrew -- Cytrynbaum, Cheryl -- Dawson, Geraldine -- de Jonge, Maretha -- Delorme, Richard -- Drmic, Irene -- Duketis, Eftichia -- Duque, Frederico -- Estes, Annette -- Farrar, Penny -- Fernandez, Bridget A -- Folstein, Susan E -- Fombonne, Eric -- Freitag, Christine M -- Gilbert, John -- Gillberg, Christopher -- Glessner, Joseph T -- Goldberg, Jeremy -- Green, Andrew -- Green, Jonathan -- Guter, Stephen J -- Hakonarson, Hakon -- Heron, Elizabeth A -- Hill, Matthew -- Holt, Richard -- Howe, Jennifer L -- Hughes, Gillian -- Hus, Vanessa -- Igliozzi, Roberta -- Kim, Cecilia -- Klauck, Sabine M -- Kolevzon, Alexander -- Korvatska, Olena -- Kustanovich, Vlad -- Lajonchere, Clara M -- Lamb, Janine A -- Laskawiec, Magdalena -- Leboyer, Marion -- Le Couteur, Ann -- Leventhal, Bennett L -- Lionel, Anath C -- Liu, Xiao-Qing -- Lord, Catherine -- Lotspeich, Linda -- Lund, Sabata C -- Maestrini, Elena -- Mahoney, William -- Mantoulan, Carine -- Marshall, Christian R -- McConachie, Helen -- McDougle, Christopher J -- McGrath, Jane -- McMahon, William M -- Merikangas, Alison -- Migita, Ohsuke -- Minshew, Nancy J -- Mirza, Ghazala K -- Munson, Jeff -- Nelson, Stanley F -- Noakes, Carolyn -- Noor, Abdul -- Nygren, Gudrun -- Oliveira, Guiomar -- Papanikolaou, Katerina -- Parr, Jeremy R -- Parrini, Barbara -- Paton, Tara -- Pickles, Andrew -- Pilorge, Marion -- Piven, Joseph -- Ponting, Chris P -- Posey, David J -- Poustka, Annemarie -- Poustka, Fritz -- Prasad, Aparna -- Ragoussis, Jiannis -- Renshaw, Katy -- Rickaby, Jessica -- Roberts, Wendy -- Roeder, Kathryn -- Roge, Bernadette -- Rutter, Michael L -- Bierut, Laura J -- Rice, John P -- Salt, Jeff -- Sansom, Katherine -- Sato, Daisuke -- Segurado, Ricardo -- Sequeira, Ana F -- Senman, Lili -- Shah, Naisha -- Sheffield, Val C -- Soorya, Latha -- Sousa, Ines -- Stein, Olaf -- Sykes, Nuala -- Stoppioni, Vera -- Strawbridge, Christina -- Tancredi, Raffaella -- Tansey, Katherine -- Thiruvahindrapduram, Bhooma -- Thompson, Ann P -- Thomson, Susanne -- Tryfon, Ana -- Tsiantis, John -- Van Engeland, Herman -- Vincent, John B -- Volkmar, Fred -- Wallace, Simon -- Wang, Kai -- Wang, Zhouzhi -- Wassink, Thomas H -- Webber, Caleb -- Weksberg, Rosanna -- Wing, Kirsty -- Wittemeyer, Kerstin -- Wood, Shawn -- Wu, Jing -- Yaspan, Brian L -- Zurawiecki, Danielle -- Zwaigenbaum, Lonnie -- Buxbaum, Joseph D -- Cantor, Rita M -- Cook, Edwin H -- Coon, Hilary -- Cuccaro, Michael L -- Devlin, Bernie -- Ennis, Sean -- Gallagher, Louise -- Geschwind, Daniel H -- Gill, Michael -- Haines, Jonathan L -- Hallmayer, Joachim -- Miller, Judith -- Monaco, Anthony P -- Nurnberger, John I Jr -- Paterson, Andrew D -- Pericak-Vance, Margaret A -- Schellenberg, Gerard D -- Szatmari, Peter -- Vicente, Astrid M -- Vieland, Veronica J -- Wijsman, Ellen M -- Scherer, Stephen W -- Sutcliffe, James S -- Betancur, Catalina -- 075491/Z/04/Wellcome Trust/United Kingdom -- AS2077/Autism Speaks/ -- AS7462/Autism Speaks/ -- G0601030/Medical Research Council/United Kingdom -- HD055751/HD/NICHD NIH HHS/ -- HD055782/HD/NICHD NIH HHS/ -- HD055784/HD/NICHD NIH HHS/ -- HD35465/HD/NICHD NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- MH061009/MH/NIMH NIH HHS/ -- MH06359/MH/NIMH NIH HHS/ -- MH066673/MH/NIMH NIH HHS/ -- MH080647/MH/NIMH NIH HHS/ -- MH081754/MH/NIMH NIH HHS/ -- MH52708/MH/NIMH NIH HHS/ -- MH55284/MH/NIMH NIH HHS/ -- MH57881/MH/NIMH NIH HHS/ -- MH66766/MH/NIMH NIH HHS/ -- NS026630/NS/NINDS NIH HHS/ -- NS042165/NS/NINDS NIH HHS/ -- NS049261/NS/NINDS NIH HHS/ -- P01 CA089392/CA/NCI NIH HHS/ -- P01 CA089392-08/CA/NCI NIH HHS/ -- P01 HD035465-01S1/HD/NICHD NIH HHS/ -- P01 NS026630/NS/NINDS NIH HHS/ -- P01 NS026630-15/NS/NINDS NIH HHS/ -- P50 HD055748/HD/NICHD NIH HHS/ -- P50 HD055748-01/HD/NICHD NIH HHS/ -- P50 HD055748-02/HD/NICHD NIH HHS/ -- P50 HD055748-03/HD/NICHD NIH HHS/ -- P50 HD055751/HD/NICHD NIH HHS/ -- P50 HD055751-01/HD/NICHD NIH HHS/ -- P50 HD055782/HD/NICHD NIH HHS/ -- P50 HD055782-04/HD/NICHD NIH HHS/ -- R01 DA013423/DA/NIDA NIH HHS/ -- R01 DA013423-05/DA/NIDA NIH HHS/ -- R01 DA019963/DA/NIDA NIH HHS/ -- R01 DA019963-01A2/DA/NIDA NIH HHS/ -- R01 DA019963-02/DA/NIDA NIH HHS/ -- R01 DA019963-03/DA/NIDA NIH HHS/ -- R01 MH052708-05/MH/NIMH NIH HHS/ -- R01 MH055284/MH/NIMH NIH HHS/ -- R01 MH055284-04/MH/NIMH NIH HHS/ -- R01 MH057881/MH/NIMH NIH HHS/ -- R01 MH057881-02/MH/NIMH NIH HHS/ -- R01 MH061009/MH/NIMH NIH HHS/ -- R01 MH061009-05/MH/NIMH NIH HHS/ -- R01 MH080647/MH/NIMH NIH HHS/ -- R01 MH080647-11/MH/NIMH NIH HHS/ -- R01 MH081754/MH/NIMH NIH HHS/ -- R01 MH081754-01/MH/NIMH NIH HHS/ -- R01 NS042165/NS/NINDS NIH HHS/ -- R01 NS042165-05/NS/NINDS NIH HHS/ -- R01 NS049261/NS/NINDS NIH HHS/ -- R01 NS049261-02/NS/NINDS NIH HHS/ -- U01 HG004422/HG/NHGRI NIH HHS/ -- U01 HG004422-02/HG/NHGRI NIH HHS/ -- U10 MH066766-05/MH/NIMH NIH HHS/ -- U19 HD035469/HD/NICHD NIH HHS/ -- U19 HD035469-06/HD/NICHD NIH HHS/ -- U19 HD035469-07/HD/NICHD NIH HHS/ -- U19 HD035469-08/HD/NICHD NIH HHS/ -- U19 HD035469-09/HD/NICHD NIH HHS/ -- U19 HD035469-10/HD/NICHD NIH HHS/ -- U54 MH066673/MH/NIMH NIH HHS/ -- U54 MH066673-05/MH/NIMH NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- Medical Research Council/United Kingdom -- England -- Nature. 2010 Jul 15;466(7304):368-72. doi: 10.1038/nature09146. Epub 2010 Jun 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20531469" target="_blank"〉PubMed〈/a〉

Description: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉