ALBERT

Description: A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) approximately 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for approximately 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751588/" 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/PMC3751588/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rietveld, Cornelius A -- Medland, Sarah E -- Derringer, Jaime -- Yang, Jian -- Esko, Tonu -- Martin, Nicolas W -- Westra, Harm-Jan -- Shakhbazov, Konstantin -- Abdellaoui, Abdel -- Agrawal, Arpana -- Albrecht, Eva -- Alizadeh, Behrooz Z -- Amin, Najaf -- Barnard, John -- Baumeister, Sebastian E -- Benke, Kelly S -- Bielak, Lawrence F -- Boatman, Jeffrey A -- Boyle, Patricia A -- Davies, Gail -- de Leeuw, Christiaan -- Eklund, Niina -- Evans, Daniel S -- Ferhmann, Rudolf -- Fischer, Krista -- Gieger, Christian -- Gjessing, Hakon K -- Hagg, Sara -- Harris, Jennifer R -- Hayward, Caroline -- Holzapfel, Christina -- Ibrahim-Verbaas, Carla A -- Ingelsson, Erik -- Jacobsson, Bo -- Joshi, Peter K -- Jugessur, Astanand -- Kaakinen, Marika -- Kanoni, Stavroula -- Karjalainen, Juha -- Kolcic, Ivana -- Kristiansson, Kati -- Kutalik, Zoltan -- Lahti, Jari -- Lee, Sang H -- Lin, Peng -- Lind, Penelope A -- Liu, Yongmei -- Lohman, Kurt -- Loitfelder, Marisa -- McMahon, George -- Vidal, Pedro Marques -- Meirelles, Osorio -- Milani, Lili -- Myhre, Ronny -- Nuotio, Marja-Liisa -- Oldmeadow, Christopher J -- Petrovic, Katja E -- Peyrot, Wouter J -- Polasek, Ozren -- Quaye, Lydia -- Reinmaa, Eva -- Rice, John P -- Rizzi, Thais S -- Schmidt, Helena -- Schmidt, Reinhold -- Smith, Albert V -- Smith, Jennifer A -- Tanaka, Toshiko -- Terracciano, Antonio -- van der Loos, Matthijs J H M -- Vitart, Veronique -- Volzke, Henry -- Wellmann, Jurgen -- Yu, Lei -- Zhao, Wei -- Allik, Juri -- Attia, John R -- Bandinelli, Stefania -- Bastardot, Francois -- Beauchamp, Jonathan -- Bennett, David A -- Berger, Klaus -- Bierut, Laura J -- Boomsma, Dorret I -- Bultmann, Ute -- Campbell, Harry -- Chabris, Christopher F -- Cherkas, Lynn -- Chung, Mina K -- Cucca, Francesco -- de Andrade, Mariza -- De Jager, Philip L -- De Neve, Jan-Emmanuel -- Deary, Ian J -- Dedoussis, George V -- Deloukas, Panos -- Dimitriou, Maria -- Eiriksdottir, Guethny -- Elderson, Martin F -- Eriksson, Johan G -- Evans, David M -- Faul, Jessica D -- Ferrucci, Luigi -- Garcia, Melissa E -- Gronberg, Henrik -- Guethnason, Vilmundur -- Hall, Per -- Harris, Juliette M -- Harris, Tamara B -- Hastie, Nicholas D -- Heath, Andrew C -- Hernandez, Dena G -- Hoffmann, Wolfgang -- Hofman, Adriaan -- Holle, Rolf -- Holliday, Elizabeth G -- Hottenga, Jouke-Jan -- Iacono, William G -- Illig, Thomas -- Jarvelin, Marjo-Riitta -- Kahonen, Mika -- Kaprio, Jaakko -- Kirkpatrick, Robert M -- Kowgier, Matthew -- Latvala, Antti -- Launer, Lenore J -- Lawlor, Debbie A -- Lehtimaki, Terho -- Li, Jingmei -- Lichtenstein, Paul -- Lichtner, Peter -- Liewald, David C -- Madden, Pamela A -- Magnusson, Patrik K E -- Makinen, Tomi E -- Masala, Marco -- McGue, Matt -- Metspalu, Andres -- Mielck, Andreas -- Miller, Michael B -- Montgomery, Grant W -- Mukherjee, Sutapa -- Nyholt, Dale R -- Oostra, Ben A -- Palmer, Lyle J -- Palotie, Aarno -- Penninx, Brenda W J H -- Perola, Markus -- Peyser, Patricia A -- Preisig, Martin -- Raikkonen, Katri -- Raitakari, Olli T -- Realo, Anu -- Ring, Susan M -- Ripatti, Samuli -- Rivadeneira, Fernando -- Rudan, Igor -- Rustichini, Aldo -- Salomaa, Veikko -- Sarin, Antti-Pekka -- Schlessinger, David -- Scott, Rodney J -- Snieder, Harold -- St Pourcain, Beate -- Starr, John M -- Sul, Jae Hoon -- Surakka, Ida -- Svento, Rauli -- Teumer, Alexander -- LifeLines Cohort Study -- Tiemeier, Henning -- van Rooij, Frank J A -- Van Wagoner, David R -- Vartiainen, Erkki -- Viikari, Jorma -- Vollenweider, Peter -- Vonk, Judith M -- Waeber, Gerard -- Weir, David R -- Wichmann, H-Erich -- Widen, Elisabeth -- Willemsen, Gonneke -- Wilson, James F -- Wright, Alan F -- Conley, Dalton -- Davey-Smith, George -- Franke, Lude -- Groenen, Patrick J F -- Hofman, Albert -- Johannesson, Magnus -- Kardia, Sharon L R -- Krueger, Robert F -- Laibson, David -- Martin, Nicholas G -- Meyer, Michelle N -- Posthuma, Danielle -- Thurik, A Roy -- Timpson, Nicholas J -- Uitterlinden, Andre G -- van Duijn, Cornelia M -- Visscher, Peter M -- Benjamin, Daniel J -- Cesarini, David -- Koellinger, Philipp D -- AA09367/AA/NIAAA NIH HHS/ -- AA11886/AA/NIAAA NIH HHS/ -- BB/F019394/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- CZB/4/710/Chief Scientist Office/United Kingdom -- DA024417/DA/NIDA NIH HHS/ -- DA029377/DA/NIDA NIH HHS/ -- DA05147/DA/NIDA NIH HHS/ -- DA13240/DA/NIDA NIH HHS/ -- ETM/55/Chief Scientist Office/United Kingdom -- F31 DA029377/DA/NIDA NIH HHS/ -- G0600705/Medical Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G9815508/Medical Research Council/United Kingdom -- K05 AA017688/AA/NIAAA NIH HHS/ -- MC_PC_U127561128/Medical Research Council/United Kingdom -- MC_UU_12013/1/Medical Research Council/United Kingdom -- MC_UU_12013/3/Medical Research Council/United Kingdom -- MC_UU_12013/5/Medical Research Council/United Kingdom -- MH016880/MH/NIMH NIH HHS/ -- MH066140/MH/NIMH NIH HHS/ -- MR/K026992/1/Medical Research Council/United Kingdom -- P01 AG005842/AG/NIA NIH HHS/ -- P01 CA089392/CA/NCI NIH HHS/ -- P01 GM099568/GM/NIGMS NIH HHS/ -- P01-AG005842/AG/NIA NIH HHS/ -- P01-AG005842-20S2/AG/NIA NIH HHS/ -- P30 AG012810/AG/NIA NIH HHS/ -- P30-AG012810/AG/NIA NIH HHS/ -- R01 AA009367/AA/NIAAA NIH HHS/ -- R01 AA011886/AA/NIAAA NIH HHS/ -- R01 DA013240/DA/NIDA NIH HHS/ -- R01 HL090620/HL/NHLBI NIH HHS/ -- R01 HL105756/HL/NHLBI NIH HHS/ -- R01 HL111314/HL/NHLBI NIH HHS/ -- R01 MH066140/MH/NIMH NIH HHS/ -- R37 DA005147/DA/NIDA NIH HHS/ -- T32 AG000186/AG/NIA NIH HHS/ -- T32 MH016880/MH/NIMH NIH HHS/ -- T32-AG000186-23/AG/NIA NIH HHS/ -- U01 AG009740/AG/NIA NIH HHS/ -- U01 DA024417/DA/NIDA NIH HHS/ -- Z01 AG001050-01/Intramural NIH HHS/ -- ZIA AG000196-03/Intramural NIH HHS/ -- ZIA AG000196-04/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 21;340(6139):1467-71. doi: 10.1126/science.1235488. Epub 2013 May 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23722424" target="_blank"〉PubMed〈/a〉

Description: Compact binary systems with neutron stars or black holes are one of the most promising sources for ground-based gravitational-wave detectors. Gravitational radiation encodes rich information about source physics; thus parameter estimation and model selection are crucial analysis steps for any detection candidate events. Detailed models of the anticipated waveforms enable inference on several parameters, such as component masses, spins, sky location and distance, that are essential for new astrophysical studies of these sources. However, accurate measurements of these parameters and discrimination of models describing the underlying physics are complicated by artifacts in the data, uncertainties in the waveform models and in the calibration of the detectors. Here we report such measurements on a selection of simulated signals added either in hardware or software to the data collected by the two LIGO instruments and the Virgo detector during their most recent joint science run, including a blind injection where the signal was not initially revealed to the collaboration. We exemplify the ability to extract information about the source physics on signals that cover the neutron-star and black-hole binary parameter space over the component mass range 1M25M and the full range of spin parameters. The cases reported in this study provide a snapshot of the status of parameter estimation in preparation for the operation of advanced detectors.

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: Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-beta precursor protein (APP) and extracellular Abeta42 and Abeta40 (the 42- and 40-residue isoforms of the amyloid-beta peptide), and knockdown of PLD3 leads to a significant increase in extracellular Abeta42 and Abeta40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050701/" 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/PMC4050701/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cruchaga, Carlos -- Karch, Celeste M -- Jin, Sheng Chih -- Benitez, Bruno A -- Cai, Yefei -- Guerreiro, Rita -- Harari, Oscar -- Norton, Joanne -- Budde, John -- Bertelsen, Sarah -- Jeng, Amanda T -- Cooper, Breanna -- Skorupa, Tara -- Carrell, David -- Levitch, Denise -- Hsu, Simon -- Choi, Jiyoon -- Ryten, Mina -- UK Brain Expression Consortium -- Hardy, John -- Trabzuni, Daniah -- Weale, Michael E -- Ramasamy, Adaikalavan -- Smith, Colin -- Sassi, Celeste -- Bras, Jose -- Gibbs, J Raphael -- Hernandez, Dena G -- Lupton, Michelle K -- Powell, John -- Forabosco, Paola -- Ridge, Perry G -- Corcoran, Christopher D -- Tschanz, Joann T -- Norton, Maria C -- Munger, Ronald G -- Schmutz, Cameron -- Leary, Maegan -- Demirci, F Yesim -- Bamne, Mikhil N -- Wang, Xingbin -- Lopez, Oscar L -- Ganguli, Mary -- Medway, Christopher -- Turton, James -- Lord, Jenny -- Braae, Anne -- Barber, Imelda -- Brown, Kristelle -- Alzheimer's Research UK Consortium -- Passmore, Peter -- Craig, David -- Johnston, Janet -- McGuinness, Bernadette -- Todd, Stephen -- Heun, Reinhard -- Kolsch, Heike -- Kehoe, Patrick G -- Hooper, Nigel M -- Vardy, Emma R L C -- Mann, David M -- Pickering-Brown, Stuart -- Kalsheker, Noor -- Lowe, James -- Morgan, Kevin -- David Smith, A -- Wilcock, Gordon -- Warden, Donald -- Holmes, Clive -- Pastor, Pau -- Lorenzo-Betancor, Oswaldo -- Brkanac, Zoran -- Scott, Erick -- Topol, Eric -- Rogaeva, Ekaterina -- Singleton, Andrew B -- Kamboh, M Ilyas -- St George-Hyslop, Peter -- Cairns, Nigel -- Morris, John C -- Kauwe, John S K -- Goate, Alison M -- 081864/Wellcome Trust/United Kingdom -- 089698/Wellcome Trust/United Kingdom -- 089703/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- 1R01AG041797/AG/NIA NIH HHS/ -- 5U24AG026395/AG/NIA NIH HHS/ -- AG005133/AG/NIA NIH HHS/ -- AG023652/AG/NIA NIH HHS/ -- AG030653/AG/NIA NIH HHS/ -- AG041718/AG/NIA NIH HHS/ -- AG07562/AG/NIA NIH HHS/ -- G0802189/Medical Research Council/United Kingdom -- G0802462/Medical Research Council/United Kingdom -- G0901254/Medical Research Council/United Kingdom -- G1100695/Medical Research Council/United Kingdom -- K01 AG046374/AG/NIA NIH HHS/ -- MC_G1000734/Medical Research Council/United Kingdom -- NIH P50 AG05681/AG/NIA NIH HHS/ -- NIH R01039700/PHS HHS/ -- P01 AG003991/AG/NIA NIH HHS/ -- P01 AG026276/AG/NIA NIH HHS/ -- P01 AG03991/AG/NIA NIH HHS/ -- P30 NS069329/NS/NINDS NIH HHS/ -- P30-NS069329/NS/NINDS NIH HHS/ -- P50 AG005133/AG/NIA NIH HHS/ -- P50 AG005681/AG/NIA NIH HHS/ -- R01 AG011380/AG/NIA NIH HHS/ -- R01 AG030653/AG/NIA NIH HHS/ -- R01 AG035083/AG/NIA NIH HHS/ -- R01 AG039700/AG/NIA NIH HHS/ -- R01 AG041718/AG/NIA NIH HHS/ -- R01 AG041797/AG/NIA NIH HHS/ -- R01 AG042611/AG/NIA NIH HHS/ -- R01 AG044546/AG/NIA NIH HHS/ -- R01-AG035083/AG/NIA NIH HHS/ -- R01-AG042611/AG/NIA NIH HHS/ -- R01-AG044546/AG/NIA NIH HHS/ -- R01-AG11380/AG/NIA NIH HHS/ -- R01-AG18712/AG/NIA NIH HHS/ -- R01-AG21136/AG/NIA NIH HHS/ -- R01AG21136/AG/NIA NIH HHS/ -- R25 DA027995/DA/NIDA NIH HHS/ -- U24 AG021886/AG/NIA NIH HHS/ -- U24 AG026395/AG/NIA NIH HHS/ -- U24AG21886/AG/NIA NIH HHS/ -- WT089698/Wellcome Trust/United Kingdom -- ZIA AG000950-11/Intramural NIH HHS/ -- ZO1 AG000950-10/AG/NIA NIH HHS/ -- ZO1AG000950-11/AG/NIA NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2014 Jan 23;505(7484):550-4. doi: 10.1038/nature12825. Epub 2013 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University 425 South Euclid Avenue, St. Louis, Missouri 63110, USA. ; 1] Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [3]. ; 1] Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2]. ; Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA. ; 1] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK [2] Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35 Room 1A1014, 35 Lincoln Drive, Bethesda, Maryland 20892, USA. ; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. ; Department of Medical and Molecular Genetics, King's College London, 16 De Crespigny Park, London SE5 8AF UK. ; MRC Sudden Death Brain Bank Project, University of Edinburgh, South Bridge, Edinburgh EH8 9YL UK. ; 1] Institute of Psychiatry, King's College London, 16 De Crespigny Park, London SE5 8AF, UK [2] Neuroimaging Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia. ; Institute of Psychiatry, King's College London, 16 De Crespigny Park, London SE5 8AF, UK. ; Istituto di Genetica delle Popolazioni - CNR, Trav. La Crucca, 3 - Reg. Baldinca - 07100 Li Punti, Sassari, Italy. ; Department of Biology, Brigham Young University, Provo, Utah 84602, USA. ; 1] Department of Mathematics and Statistics, Utah State University, Logan, Utah 84322, USA [2] Center for Epidemiologic Studies, Utah State University, Logan, Utah 84322, USA. ; 1] Center for Epidemiologic Studies, Utah State University, Logan, Utah 84322, USA [2] Department of Psychology, Utah State University, Logan, Utah 84322, USA. ; 1] Center for Epidemiologic Studies, Utah State University, Logan, Utah 84322, USA [2] Department of Psychology, Utah State University, Logan, Utah 84322, USA [3] Department of Family Consumer and Human Development, Utah State University, Logan, Utah 84322, USA. ; 1] Department of Family Consumer and Human Development, Utah State University, Logan, Utah 84322, USA [2] Department of Nutrition, Dietetics, and Food Sciences, Utah State University, Logan, Utah 84322, USA. ; Department of Human Genetics, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA. ; 1] Alzheimer's Disease Research Center, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA [2] Department of Neurology, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA. ; Department of Psychiatry, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA. ; Human Genetics, School of Molecular Medical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. ; Queen's University Belfast, University Road, Belfast BT7 1NN, UK. ; Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3NE, UK. ; University of Bonn, Regina-Pacis-Weg 3, 53113 Bonn, Germany. ; University of Bristol, Tyndall Avenue, Bristol, City of Bristol BS8 1TH, UK. ; University of Leeds, Woodhouse Lane, Leeds, West Yorkshire LS2 9JT, UK. ; University of Newcastle, Newcastle upon Tyne, Tyne and Wear NE1 7RU, UK. ; University of Manchester, Oxford Road, Manchester, Greater Manchester M13 9PL, UK. ; University of Oxford (OPTIMA), Wellington Square, Oxford OX1 2JD, UK. ; 1] Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Avenida Pio XII, 55. 31008 Pamplona, Navarra, Spain [2] Department of Neurology, Clinica Universidad de Navarra, School of Medicine, University of Navarra Avenida Pio XII, 36. 31008 Pamplona, Spain [3] CIBERNED, Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Spain. ; Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra, Avenida Pio XII, 55. 31008 Pamplona, Navarra, Spain. ; University of Washington, 325 Ninth Avenue, Seattle, Washington 98104-2499, USA. ; The Scripps Research Institute, La Jolla, California 3344 North Torrey Pines Court, La Jolla, California 92037, USA. ; Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Avenue, Toronto, Ontario M5T 2S8, Canada. ; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35 Room 1A1014, 35 Lincoln Drive, Bethesda, Maryland 20892, USA. ; 1] Department of Human Genetics, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA [2] Alzheimer's Disease Research Center, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA [3] Department of Neurology, University of Pittsburgh, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA. ; 1] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Avenue, Toronto, Ontario M5T 2S8, Canada [2] Cambridge Institute for Medical Research, and the Department of Clinical Neurosciences, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. ; 1] Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Pathology and Immunology, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA. ; 1] Pathology and Immunology, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Department of Neurology, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [3] Knight ADRC, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA. ; 1] Department of Psychiatry, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [2] Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [3] Department of Neurology, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [4] Knight ADRC, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA [5] Department of Genetics, Washington University, 425 South Euclid Avenue, St. Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24336208" target="_blank"〉PubMed〈/a〉

Description: The Rocknest aeolian deposit is similar to aeolian features analyzed by the Mars Exploration Rovers (MER) Spirit and Opportunity. The fraction of sand 〈150 micron in size contains approx. 55% crystalline material consistent with a basaltic heritage, and approx. 45% X-ray amorphous material. The amorphous component of Rocknest is Fe-rich and Si-poor, and is the host of the volatiles (H2O, O2, SO2, CO2, and Cl) detected by the Surface Analysis at Mars (SAM) instrument and of the fine-grained nanophase oxide (npOx) component first described from basaltic soils analyzed by MER. The similarity between soils and aeolian materials analyzed at Gusev crater, Meridiani Planum and Gale crater implies locally sourced, globally similar basaltic materials, or globally and regionally sourced basaltic components deposited locally at all three locations.

Description: Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer. These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919509/" 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/PMC3919509/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawrence, Michael S -- Stojanov, Petar -- Polak, Paz -- Kryukov, Gregory V -- Cibulskis, Kristian -- Sivachenko, Andrey -- Carter, Scott L -- Stewart, Chip -- Mermel, Craig H -- Roberts, Steven A -- Kiezun, Adam -- Hammerman, Peter S -- McKenna, Aaron -- Drier, Yotam -- Zou, Lihua -- Ramos, Alex H -- Pugh, Trevor J -- Stransky, Nicolas -- Helman, Elena -- Kim, Jaegil -- Sougnez, Carrie -- Ambrogio, Lauren -- Nickerson, Elizabeth -- Shefler, Erica -- Cortes, Maria L -- Auclair, Daniel -- Saksena, Gordon -- Voet, Douglas -- Noble, Michael -- DiCara, Daniel -- Lin, Pei -- Lichtenstein, Lee -- Heiman, David I -- Fennell, Timothy -- Imielinski, Marcin -- Hernandez, Bryan -- Hodis, Eran -- Baca, Sylvan -- Dulak, Austin M -- Lohr, Jens -- Landau, Dan-Avi -- Wu, Catherine J -- Melendez-Zajgla, Jorge -- Hidalgo-Miranda, Alfredo -- Koren, Amnon -- McCarroll, Steven A -- Mora, Jaume -- Lee, Ryan S -- Crompton, Brian -- Onofrio, Robert -- Parkin, Melissa -- Winckler, Wendy -- Ardlie, Kristin -- Gabriel, Stacey B -- Roberts, Charles W M -- Biegel, Jaclyn A -- Stegmaier, Kimberly -- Bass, Adam J -- Garraway, Levi A -- Meyerson, Matthew -- Golub, Todd R -- Gordenin, Dmitry A -- Sunyaev, Shamil -- Lander, Eric S -- Getz, Gad -- ES065073/ES/NIEHS NIH HHS/ -- T32 CA009172/CA/NCI NIH HHS/ -- T32 CA009216/CA/NCI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- U24 CA143845/CA/NCI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- England -- Nature. 2013 Jul 11;499(7457):214-8. doi: 10.1038/nature12213. Epub 2013 Jun 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23770567" target="_blank"〉PubMed〈/a〉

Description: Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the approximately 4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 x 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 x 10(-10) and P = 7.8 x 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P 〈 10(-8)), as has been reported previously for autism spectrum disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773011/" 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/PMC3773011/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Epi4K Consortium -- Epilepsy Phenome/Genome Project -- Allen, Andrew S -- Berkovic, Samuel F -- Cossette, Patrick -- Delanty, Norman -- Dlugos, Dennis -- Eichler, Evan E -- Epstein, Michael P -- Glauser, Tracy -- Goldstein, David B -- Han, Yujun -- Heinzen, Erin L -- Hitomi, Yuki -- Howell, Katherine B -- Johnson, Michael R -- Kuzniecky, Ruben -- Lowenstein, Daniel H -- Lu, Yi-Fan -- Madou, Maura R Z -- Marson, Anthony G -- Mefford, Heather C -- Esmaeeli Nieh, Sahar -- O'Brien, Terence J -- Ottman, Ruth -- Petrovski, Slave -- Poduri, Annapurna -- Ruzzo, Elizabeth K -- Scheffer, Ingrid E -- Sherr, Elliott H -- Yuskaitis, Christopher J -- Abou-Khalil, Bassel -- Alldredge, Brian K -- Bautista, Jocelyn F -- Boro, Alex -- Cascino, Gregory D -- Consalvo, Damian -- Crumrine, Patricia -- Devinsky, Orrin -- Fiol, Miguel -- Fountain, Nathan B -- French, Jacqueline -- Friedman, Daniel -- Geller, Eric B -- Glynn, Simon -- Haut, Sheryl R -- Hayward, Jean -- Helmers, Sandra L -- Joshi, Sucheta -- Kanner, Andres -- Kirsch, Heidi E -- Knowlton, Robert C -- Kossoff, Eric H -- Kuperman, Rachel -- McGuire, Shannon M -- Motika, Paul V -- Novotny, Edward J -- Paolicchi, Juliann M -- Parent, Jack M -- Park, Kristen -- Shellhaas, Renee A -- Shih, Jerry J -- Singh, Rani -- Sirven, Joseph -- Smith, Michael C -- Sullivan, Joseph -- Lin Thio, Liu -- Venkat, Anu -- Vining, Eileen P G -- Von Allmen, Gretchen K -- Weisenberg, Judith L -- Widdess-Walsh, Peter -- Winawer, Melodie R -- 1RC2NS070342/NS/NINDS NIH HHS/ -- NS053998/NS/NINDS NIH HHS/ -- NS077274/NS/NINDS NIH HHS/ -- NS077276/NS/NINDS NIH HHS/ -- NS077303/NS/NINDS NIH HHS/ -- NS077364/NS/NINDS NIH HHS/ -- R56AI098588/AI/NIAID NIH HHS/ -- U01 NS053998/NS/NINDS NIH HHS/ -- U01 NS077274/NS/NINDS NIH HHS/ -- U01 NS077276/NS/NINDS NIH HHS/ -- U01 NS077303/NS/NINDS NIH HHS/ -- U01 NS077364/NS/NINDS NIH HHS/ -- U01AI067854/AI/NIAID NIH HHS/ -- UL1 TR000005/TR/NCATS NIH HHS/ -- England -- Nature. 2013 Sep 12;501(7466):217-21. doi: 10.1038/nature12439. Epub 2013 Aug 11.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23934111" target="_blank"〉PubMed〈/a〉

Description: The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633110/" 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/PMC3633110/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Amemiya, Chris T -- Alfoldi, Jessica -- Lee, Alison P -- Fan, Shaohua -- Philippe, Herve -- Maccallum, Iain -- Braasch, Ingo -- Manousaki, Tereza -- Schneider, Igor -- Rohner, Nicolas -- Organ, Chris -- Chalopin, Domitille -- Smith, Jeramiah J -- Robinson, Mark -- Dorrington, Rosemary A -- Gerdol, Marco -- Aken, Bronwen -- Biscotti, Maria Assunta -- Barucca, Marco -- Baurain, Denis -- Berlin, Aaron M -- Blatch, Gregory L -- Buonocore, Francesco -- Burmester, Thorsten -- Campbell, Michael S -- Canapa, Adriana -- Cannon, John P -- Christoffels, Alan -- De Moro, Gianluca -- Edkins, Adrienne L -- Fan, Lin -- Fausto, Anna Maria -- Feiner, Nathalie -- Forconi, Mariko -- Gamieldien, Junaid -- Gnerre, Sante -- Gnirke, Andreas -- Goldstone, Jared V -- Haerty, Wilfried -- Hahn, Mark E -- Hesse, Uljana -- Hoffmann, Steve -- Johnson, Jeremy -- Karchner, Sibel I -- Kuraku, Shigehiro -- Lara, Marcia -- Levin, Joshua Z -- Litman, Gary W -- Mauceli, Evan -- Miyake, Tsutomu -- Mueller, M Gail -- Nelson, David R -- Nitsche, Anne -- Olmo, Ettore -- Ota, Tatsuya -- Pallavicini, Alberto -- Panji, Sumir -- Picone, Barbara -- Ponting, Chris P -- Prohaska, Sonja J -- Przybylski, Dariusz -- Saha, Nil Ratan -- Ravi, Vydianathan -- Ribeiro, Filipe J -- Sauka-Spengler, Tatjana -- Scapigliati, Giuseppe -- Searle, Stephen M J -- Sharpe, Ted -- Simakov, Oleg -- Stadler, Peter F -- Stegeman, John J -- Sumiyama, Kenta -- Tabbaa, Diana -- Tafer, Hakim -- Turner-Maier, Jason -- van Heusden, Peter -- White, Simon -- Williams, Louise -- Yandell, Mark -- Brinkmann, Henner -- Volff, Jean-Nicolas -- Tabin, Clifford J -- Shubin, Neil -- Schartl, Manfred -- Jaffe, David B -- Postlethwait, John H -- Venkatesh, Byrappa -- Di Palma, Federica -- Lander, Eric S -- Meyer, Axel -- Lindblad-Toh, Kerstin -- 095908/Wellcome Trust/United Kingdom -- MC_U137761446/Medical Research Council/United Kingdom -- P42 ES007381/ES/NIEHS NIH HHS/ -- R01 ES006272/ES/NIEHS NIH HHS/ -- R01 HG003474/HG/NHGRI NIH HHS/ -- R01 OD011116/OD/NIH HHS/ -- R24 OD011199/OD/NIH HHS/ -- R24 RR032670/RR/NCRR NIH HHS/ -- R37 HD032443/HD/NICHD NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- England -- Nature. 2013 Apr 18;496(7445):311-6. doi: 10.1038/nature12027.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics Program, Benaroya Research Institute, Seattle, Washington 98101, USA. camemiya@benaroyaresearch.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23598338" target="_blank"〉PubMed〈/a〉

Description: Statins are prescribed widely to lower plasma low-density lipoprotein (LDL) concentrations and cardiovascular disease risk and have been shown to have beneficial effects in a broad range of patients. However, statins are associated with an increased risk, albeit small, of clinical myopathy and type 2 diabetes. Despite evidence for substantial genetic influence on LDL concentrations, pharmacogenomic trials have failed to identify genetic variations with large effects on either statin efficacy or toxicity, and have produced little information regarding mechanisms that modulate statin response. Here we identify a downstream target of statin treatment by screening for the effects of in vitro statin exposure on genetic associations with gene expression levels in lymphoblastoid cell lines derived from 480 participants of a clinical trial of simvastatin treatment. This analysis identified six expression quantitative trait loci (eQTLs) that interacted with simvastatin exposure, including rs9806699, a cis-eQTL for the gene glycine amidinotransferase (GATM) that encodes the rate-limiting enzyme in creatine synthesis. We found this locus to be associated with incidence of statin-induced myotoxicity in two separate populations (meta-analysis odds ratio = 0.60). Furthermore, we found that GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional link between statin-mediated lowering of cholesterol and susceptibility to statin-induced myopathy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933266/" 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/PMC3933266/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mangravite, Lara M -- Engelhardt, Barbara E -- Medina, Marisa W -- Smith, Joshua D -- Brown, Christopher D -- Chasman, Daniel I -- Mecham, Brigham H -- Howie, Bryan -- Shim, Heejung -- Naidoo, Devesh -- Feng, QiPing -- Rieder, Mark J -- Chen, Yii-Der I -- Rotter, Jerome I -- Ridker, Paul M -- Hopewell, Jemma C -- Parish, Sarah -- Armitage, Jane -- Collins, Rory -- Wilke, Russell A -- Nickerson, Deborah A -- Stephens, Matthew -- Krauss, Ronald M -- HG002585/HG/NHGRI NIH HHS/ -- K99/R00HG006265/HG/NHGRI NIH HHS/ -- MC_U137686853/Medical Research Council/United Kingdom -- P30 DK063491/DK/NIDDK NIH HHS/ -- R00 HG006265/HG/NHGRI NIH HHS/ -- R01 HG002585/HG/NHGRI NIH HHS/ -- R01 HL104133/HL/NHLBI NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL69757/HL/NHLBI NIH HHS/ -- UL1 TR000124/TR/NCATS NIH HHS/ -- British Heart Foundation/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2013 Oct 17;502(7471):377-80. doi: 10.1038/nature12508. Epub 2013 Aug 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sage Bionetworks, 1100 Fairview Avenue North, Seattle, Washington 98109, USA. lara.mangravite@sagebase.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23995691" target="_blank"〉PubMed〈/a〉

Description: Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822165/" 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/PMC3822165/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Prado-Martinez, Javier -- Sudmant, Peter H -- Kidd, Jeffrey M -- Li, Heng -- Kelley, Joanna L -- Lorente-Galdos, Belen -- Veeramah, Krishna R -- Woerner, August E -- O'Connor, Timothy D -- Santpere, Gabriel -- Cagan, Alexander -- Theunert, Christoph -- Casals, Ferran -- Laayouni, Hafid -- Munch, Kasper -- Hobolth, Asger -- Halager, Anders E -- Malig, Maika -- Hernandez-Rodriguez, Jessica -- Hernando-Herraez, Irene -- Prufer, Kay -- Pybus, Marc -- Johnstone, Laurel -- Lachmann, Michael -- Alkan, Can -- Twigg, Dorina -- Petit, Natalia -- Baker, Carl -- Hormozdiari, Fereydoun -- Fernandez-Callejo, Marcos -- Dabad, Marc -- Wilson, Michael L -- Stevison, Laurie -- Camprubi, Cristina -- Carvalho, Tiago -- Ruiz-Herrera, Aurora -- Vives, Laura -- Mele, Marta -- Abello, Teresa -- Kondova, Ivanela -- Bontrop, Ronald E -- Pusey, Anne -- Lankester, Felix -- Kiyang, John A -- Bergl, Richard A -- Lonsdorf, Elizabeth -- Myers, Simon -- Ventura, Mario -- Gagneux, Pascal -- Comas, David -- Siegismund, Hans -- Blanc, Julie -- Agueda-Calpena, Lidia -- Gut, Marta -- Fulton, Lucinda -- Tishkoff, Sarah A -- Mullikin, James C -- Wilson, Richard K -- Gut, Ivo G -- Gonder, Mary Katherine -- Ryder, Oliver A -- Hahn, Beatrice H -- Navarro, Arcadi -- Akey, Joshua M -- Bertranpetit, Jaume -- Reich, David -- Mailund, Thomas -- Schierup, Mikkel H -- Hvilsom, Christina -- Andres, Aida M -- Wall, Jeffrey D -- Bustamante, Carlos D -- Hammer, Michael F -- Eichler, Evan E -- Marques-Bonet, Tomas -- 090532/Wellcome Trust/United Kingdom -- 260372/European Research Council/International -- DP1 ES022577/ES/NIEHS NIH HHS/ -- DP1ES022577-04/DP/NCCDPHP CDC HHS/ -- GM100233/GM/NIGMS NIH HHS/ -- HG002385/HG/NHGRI NIH HHS/ -- R01 GM095882/GM/NIGMS NIH HHS/ -- R01 GM100233/GM/NIGMS NIH HHS/ -- R01 HG002385/HG/NHGRI NIH HHS/ -- R01_HG005226/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jul 25;499(7459):471-5. doi: 10.1038/nature12228. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Biologia Evolutiva, CSIC-Universitat Pompeu Fabra, PRBB, Doctor Aiguader 88, Barcelona, Catalonia 08003, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823723" target="_blank"〉PubMed〈/a〉