ALBERT

Description: Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs. This structure reveals blocks of limited haplotype diversity in which more than 80% of a global human sample can typically be characterized by only three common haplotypes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Patil, N -- Berno, A J -- Hinds, D A -- Barrett, W A -- Doshi, J M -- Hacker, C R -- Kautzer, C R -- Lee, D H -- Marjoribanks, C -- McDonough, D P -- Nguyen, B T -- Norris, M C -- Sheehan, J B -- Shen, N -- Stern, D -- Stokowski, R P -- Thomas, D J -- Trulson, M O -- Vyas, K R -- Frazer, K A -- Fodor, S P -- Cox, D R -- New York, N.Y. -- Science. 2001 Nov 23;294(5547):1719-23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Perlegen Sciences, Inc., 2021 Stierlin Court, Mountain View, CA 94043, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11721056" target="_blank"〉PubMed〈/a〉

Description: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF 〈/= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755714/" 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/PMC4755714/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Hou-Feng -- Forgetta, Vincenzo -- Hsu, Yi-Hsiang -- Estrada, Karol -- Rosello-Diez, Alberto -- Leo, Paul J -- Dahia, Chitra L -- Park-Min, Kyung Hyun -- Tobias, Jonathan H -- Kooperberg, Charles -- Kleinman, Aaron -- Styrkarsdottir, Unnur -- Liu, Ching-Ti -- Uggla, Charlotta -- Evans, Daniel S -- Nielson, Carrie M -- Walter, Klaudia -- Pettersson-Kymmer, Ulrika -- McCarthy, Shane -- Eriksson, Joel -- Kwan, Tony -- Jhamai, Mila -- Trajanoska, Katerina -- Memari, Yasin -- Min, Josine -- Huang, Jie -- Danecek, Petr -- Wilmot, Beth -- Li, Rui -- Chou, Wen-Chi -- Mokry, Lauren E -- Moayyeri, Alireza -- Claussnitzer, Melina -- Cheng, Chia-Ho -- Cheung, Warren -- Medina-Gomez, Carolina -- Ge, Bing -- Chen, Shu-Huang -- Choi, Kwangbom -- Oei, Ling -- Fraser, James -- Kraaij, Robert -- Hibbs, Matthew A -- Gregson, Celia L -- Paquette, Denis -- Hofman, Albert -- Wibom, Carl -- Tranah, Gregory J -- Marshall, Mhairi -- Gardiner, Brooke B -- Cremin, Katie -- Auer, Paul -- Hsu, Li -- Ring, Sue -- Tung, Joyce Y -- Thorleifsson, Gudmar -- Enneman, Anke W -- van Schoor, Natasja M -- de Groot, Lisette C P G M -- van der Velde, Nathalie -- Melin, Beatrice -- Kemp, John P -- Christiansen, Claus -- Sayers, Adrian -- Zhou, Yanhua -- Calderari, Sophie -- van Rooij, Jeroen -- Carlson, Chris -- Peters, Ulrike -- Berlivet, Soizik -- Dostie, Josee -- Uitterlinden, Andre G -- Williams, Stephen R -- Farber, Charles -- Grinberg, Daniel -- LaCroix, Andrea Z -- Haessler, Jeff -- Chasman, Daniel I -- Giulianini, Franco -- Rose, Lynda M -- Ridker, Paul M -- Eisman, John A -- Nguyen, Tuan V -- Center, Jacqueline R -- Nogues, Xavier -- Garcia-Giralt, Natalia -- Launer, Lenore L -- Gudnason, Vilmunder -- Mellstrom, Dan -- Vandenput, Liesbeth -- Amin, Najaf -- van Duijn, Cornelia M -- Karlsson, Magnus K -- Ljunggren, Osten -- Svensson, Olle -- Hallmans, Goran -- Rousseau, Francois -- Giroux, Sylvie -- Bussiere, Johanne -- Arp, Pascal P -- Koromani, Fjorda -- Prince, Richard L -- Lewis, Joshua R -- Langdahl, Bente L -- Hermann, A Pernille -- Jensen, Jens-Erik B -- Kaptoge, Stephen -- Khaw, Kay-Tee -- Reeve, Jonathan -- Formosa, Melissa M -- Xuereb-Anastasi, Angela -- Akesson, Kristina -- McGuigan, Fiona E -- Garg, Gaurav -- Olmos, Jose M -- Zarrabeitia, Maria T -- Riancho, Jose A -- Ralston, Stuart H -- Alonso, Nerea -- Jiang, Xi -- Goltzman, David -- Pastinen, Tomi -- Grundberg, Elin -- Gauguier, Dominique -- Orwoll, Eric S -- Karasik, David -- Davey-Smith, George -- AOGC Consortium -- Smith, Albert V -- Siggeirsdottir, Kristin -- Harris, Tamara B -- Zillikens, M Carola -- van Meurs, Joyce B J -- Thorsteinsdottir, Unnur -- Maurano, Matthew T -- Timpson, Nicholas J -- Soranzo, Nicole -- Durbin, Richard -- Wilson, Scott G -- Ntzani, Evangelia E -- Brown, Matthew A -- Stefansson, Kari -- Hinds, David A -- Spector, Tim -- Cupples, L Adrienne -- Ohlsson, Claes -- Greenwood, Celia M T -- UK10K Consortium -- Jackson, Rebecca D -- Rowe, David W -- Loomis, Cynthia A -- Evans, David M -- Ackert-Bicknell, Cheryl L -- Joyner, Alexandra L -- Duncan, Emma L -- Kiel, Douglas P -- Rivadeneira, Fernando -- Richards, J Brent -- G1000143/Medical Research Council/United Kingdom -- K01 AR062655/AR/NIAMS NIH HHS/ -- MC_UU_12013/3/Medical Research Council/United Kingdom -- R01 AG005394/AG/NIA NIH HHS/ -- R01 AG005407/AG/NIA NIH HHS/ -- R01 AG027574/AG/NIA NIH HHS/ -- R01 AG027576/AG/NIA NIH HHS/ -- R01 AR035582/AR/NIAMS NIH HHS/ -- R01 AR035583/AR/NIAMS NIH HHS/ -- RC2 AR058973/AR/NIAMS NIH HHS/ -- U01 AG018197/AG/NIA NIH HHS/ -- U01 AG042140/AG/NIA NIH HHS/ -- U01 AG042143/AG/NIA NIH HHS/ -- U01 AR045580/AR/NIAMS NIH HHS/ -- U01 AR045583/AR/NIAMS NIH HHS/ -- U01 AR045614/AR/NIAMS NIH HHS/ -- U01 AR045632/AR/NIAMS NIH HHS/ -- U01 AR045647/AR/NIAMS NIH HHS/ -- U01 AR045654/AR/NIAMS NIH HHS/ -- U01 AR066160/AR/NIAMS NIH HHS/ -- England -- Nature. 2015 Oct 1;526(7571):112-7. doi: 10.1038/nature14878. Epub 2015 Sep 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montreal H3A 1A2, Canada. ; Department of Medicine, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal H3T 1E2, Canada. ; Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts 02131, USA. ; Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Broad Institute of MIT and Harvard, Boston, Massachusetts 02115, USA. ; Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3015GE, The Netherlands. ; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Developmental Biology Program, Sloan Kettering Institute, New York, New York 10065, USA. ; The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane 4102, Australia. ; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York 10065, USA. ; Tissue Engineering, Regeneration and Repair Program, Hospital for Special Surgery, New York 10021, USA. ; Rheumatology Divison, Hospital for Special Surgery New York, New York 10021, USA. ; School of Clinical Science, University of Bristol, Bristol BS10 5NB, UK. ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. ; Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; Department of Research, 23andMe, Mountain View, California 94041, USA. ; Department of Population Genomics, deCODE Genetics, Reykjavik IS-101, Iceland. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden. ; California Pacific Medical Center Research Institute, San Francisco, California 94158, USA. ; Department of Public Health and Preventive Medicine, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Bone &Mineral Unit, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK. ; Departments of Pharmacology and Clinical Neurosciences, Umea University, Umea S-901 87, Sweden. ; Department of Public Health and Clinical Medicine, Umea University, Umea SE-901 87, Sweden. ; Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden. ; McGill University and Genome Quebec Innovation Centre, Montreal H3A 0G1, Canada. ; Department of Epidemiology, Erasmus Medical Center, Rotterdam 3015GE, The Netherlands. ; Oregon Clinical and Translational Research Institute, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Department of Medical and Clinical Informatics, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Farr Institute of Health Informatics Research, University College London, London NW1 2DA, UK. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. ; Department of Human Genetics, McGill University, Montreal H3A 1B1, Canada. ; Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden 2300RC, The Netherlands. ; Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642, USA. ; Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montreal H3G 1Y6, Canada. ; Department of Computer Science, Trinity University, San Antonio, Texas 78212, USA. ; Musculoskeletal Research Unit, University of Bristol, Bristol BS10 5NB, UK. ; Department of Radiation Sciences, Umea University, Umea S-901 87, Sweden. ; School of Public Health, University of Wisconsin, Milwaukee, Wisconsin 53726, USA. ; School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK. ; Department of Statistics, deCODE Genetics, Reykjavik IS-101, Iceland. ; Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam 1007 MB, The Netherlands. ; Department of Human Nutrition, Wageningen University, Wageningen 6700 EV, The Netherlands. ; Department of Internal Medicine, Section Geriatrics, Academic Medical Center, Amsterdam 1105, The Netherlands. ; Nordic Bioscience, Herlev 2730, Denmark. ; Cordeliers Research Centre, INSERM UMRS 1138, Paris 75006, France. ; Institute of Cardiometabolism and Nutrition, University Pierre &Marie Curie, Paris 75013, France. ; Departments of Medicine (Cardiovascular Medicine), Centre for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22908, USA. ; Department of Genetics, University of Barcelona, Barcelona 08028, Spain. ; U-720, Centre for Biomedical Network Research on Rare Diseases (CIBERER), Barcelona 28029, Spain. ; Department of Human Molecular Genetics, The Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona 08028, Spain. ; Women's Health Center of Excellence Family Medicine and Public Health, University of California - San Diego, San Diego, California 92093, USA. ; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. ; Osteoporosis &Bone Biology Program, Garvan Institute of Medical Research, Sydney 2010, Australia. ; School of Medicine Sydney, University of Notre Dame Australia, Sydney 6959, Australia. ; St. Vincent's Hospital &Clinical School, NSW University, Sydney 2010, Australia. ; Musculoskeletal Research Group, Institut Hospital del Mar d'Investigacions Mediques, Barcelona 08003, Spain. ; Cooperative Research Network on Aging and Fragility (RETICEF), Institute of Health Carlos III, 28029, Spain. ; Department of Internal Medicine, Hospital del Mar, Universitat Autonoma de Barcelona, Barcelona 08193, Spain. ; Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Icelandic Heart Association, Kopavogur IS-201, Iceland. ; Faculty of Medicine, University of Iceland, Reykjavik IS-101, Iceland. ; Genetic epidemiology unit, Department of Epidemiology, Erasmus MC, Rotterdam 3000CA, The Netherlands. ; Department of Orthopaedics, Skane University Hospital Malmo 205 02, Sweden. ; Department of Medical Sciences, University of Uppsala, Uppsala 751 85, Sweden. ; Department of Surgical and Perioperative Sciences, Umea Unviersity, Umea 901 85, Sweden. ; Department of Molecular Biology, Medical Biochemistry and Pathology, Universite Laval, Quebec City G1V 0A6, Canada. ; Axe Sante des Populations et Pratiques Optimales en Sante, Centre de recherche du CHU de Quebec, Quebec City G1V 4G2, Canada. ; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands 6009, Australia. ; Department of Medicine, University of Western Australia, Perth 6009, Australia. ; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus C 8000, Denmark. ; Department of Endocrinology, Odense University Hospital, Odense C 5000, Denmark. ; Department of Endocrinology, Hvidovre University Hospital, Hvidovre 2650, Denmark. ; Clinical Gerontology Unit, University of Cambridge, Cambridge CB2 2QQ, UK. ; Medicine and Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. ; Institute of Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford OX3 7LD, UK. ; Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida MSD 2080, Malta. ; Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmo, Lund University, 205 02, Sweden. ; Department of Medicine and Psychiatry, University of Cantabria, Santander 39011, Spain. ; Department of Internal Medicine, Hospital U.M. Valdecilla- IDIVAL, Santander 39008, Spain. ; Department of Legal Medicine, University of Cantabria, Santander 39011, Spain. ; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Department of Reconstructive Sciences, College of Dental Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. ; Department of Medicine and Physiology, McGill University, Montreal H4A 3J1, Canada. ; Department of Medicine, Oregon Health &Science University, Portland, Oregon 97239, USA. ; Faculty of Medicine in the Galilee, Bar-Ilan University, Safed 13010, Israel. ; Laboratory of Epidemiology, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; School of Medicine and Pharmacology, University of Western Australia, Crawley 6009, Australia. ; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece. ; Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, Rhode Island 02903, USA. ; deCODE Genetics, Reykjavik IS-101, Iceland. ; Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal H3A 1A2, Canada. ; Department of Oncology, Gerald Bronfman Centre, McGill University, Montreal H2W 1S6, Canada. ; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio 43210, USA. ; The Ronald O. Perelman Department of Dermatology and Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA. ; Department of Diabetes and Endocrinology, Royal Brisbane and Women's Hospital, Brisbane 4029, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26367794" target="_blank"〉PubMed〈/a〉

Description: Coronary heart disease (CHD) is a major cause of death in Western countries. We used genome-wide association scanning to identify a 58-kilobase interval on chromosome 9p21 that was consistently associated with CHD in six independent samples (more than 23,000 participants) from four Caucasian populations. This interval, which is located near the CDKN2A and CDKN2B genes, contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension, or diabetes. Homozygotes for the risk allele make up 20 to 25% of Caucasians and have a approximately 30 to 40% increased risk of CHD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711874/" 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/PMC2711874/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McPherson, Ruth -- Pertsemlidis, Alexander -- Kavaslar, Nihan -- Stewart, Alexandre -- Roberts, Robert -- Cox, David R -- Hinds, David A -- Pennacchio, Len A -- Tybjaerg-Hansen, Anne -- Folsom, Aaron R -- Boerwinkle, Eric -- Hobbs, Helen H -- Cohen, Jonathan C -- HL-066681/HL/NHLBI NIH HHS/ -- HL-082896/HL/NHLBI NIH HHS/ -- R01 HL082896/HL/NHLBI NIH HHS/ -- R01 HL082896-02/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2007 Jun 8;316(5830):1488-91. Epub 2007 May 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cardiology, University of Ottawa Heart Institute, Ottawa K1Y4W7, Canada. rmcpherson@ottawaheart.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17478681" target="_blank"〉PubMed〈/a〉

Description: Individual differences in DNA sequence are the genetic basis of human variability. We have characterized whole-genome patterns of common human DNA variation by genotyping 1,586,383 single-nucleotide polymorphisms (SNPs) in 71 Americans of European, African, and Asian ancestry. Our results indicate that these SNPs capture most common genetic variation as a result of linkage disequilibrium, the correlation among common SNP alleles. We observe a strong correlation between extended regions of linkage disequilibrium and functional genomic elements. Our data provide a tool for exploring many questions that remain regarding the causal role of common human DNA variation in complex human traits and for investigating the nature of genetic variation within and between human populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hinds, David A -- Stuve, Laura L -- Nilsen, Geoffrey B -- Halperin, Eran -- Eskin, Eleazar -- Ballinger, Dennis G -- Frazer, Kelly A -- Cox, David R -- New York, N.Y. -- Science. 2005 Feb 18;307(5712):1072-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Perlegen Sciences Inc., 2021 Stierlin Court, Mountain View, CA 94043, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15718463" target="_blank"〉PubMed〈/a〉

Description: The genomes of individuals from the same species vary in sequence as a result of different evolutionary processes. To examine the patterns of, and the forces shaping, sequence variation in Arabidopsis thaliana, we performed high-density array resequencing of 20 diverse strains (accessions). More than 1 million nonredundant single-nucleotide polymorphisms (SNPs) were identified at moderate false discovery rates (FDRs), and approximately 4% of the genome was identified as being highly dissimilar or deleted relative to the reference genome sequence. Patterns of polymorphism are highly nonrandom among gene families, with genes mediating interaction with the biotic environment having exceptional polymorphism levels. At the chromosomal scale, regional variation in polymorphism was readily apparent. A scan for recent selective sweeps revealed several candidate regions, including a notable example in which almost all variation was removed in a 500-kilobase window. Analyzing the polymorphisms we describe in larger sets of accessions will enable a detailed understanding of forces shaping population-wide sequence variation in A. thaliana.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clark, Richard M -- Schweikert, Gabriele -- Toomajian, Christopher -- Ossowski, Stephan -- Zeller, Georg -- Shinn, Paul -- Warthmann, Norman -- Hu, Tina T -- Fu, Glenn -- Hinds, David A -- Chen, Huaming -- Frazer, Kelly A -- Huson, Daniel H -- Scholkopf, Bernhard -- Nordborg, Magnus -- Ratsch, Gunnar -- Ecker, Joseph R -- Weigel, Detlef -- New York, N.Y. -- Science. 2007 Jul 20;317(5836):338-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17641193" target="_blank"〉PubMed〈/a〉

Description: Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okbay, Aysu -- Beauchamp, Jonathan P -- Fontana, Mark Alan -- Lee, James J -- Pers, Tune H -- Rietveld, Cornelius A -- Turley, Patrick -- Chen, Guo-Bo -- Emilsson, Valur -- Meddens, S Fleur W -- Oskarsson, Sven -- Pickrell, Joseph K -- Thom, Kevin -- Timshel, Pascal -- de Vlaming, Ronald -- Abdellaoui, Abdel -- Ahluwalia, Tarunveer S -- Bacelis, Jonas -- Baumbach, Clemens -- Bjornsdottir, Gyda -- Brandsma, Johannes H -- Pina Concas, Maria -- Derringer, Jaime -- Furlotte, Nicholas A -- Galesloot, Tessel E -- Girotto, Giorgia -- Gupta, Richa -- Hall, Leanne M -- Harris, Sarah E -- Hofer, Edith -- Horikoshi, Momoko -- Huffman, Jennifer E -- Kaasik, Kadri -- Kalafati, Ioanna P -- Karlsson, Robert -- Kong, Augustine -- Lahti, Jari -- van der Lee, Sven J -- deLeeuw, Christiaan -- Lind, Penelope A -- Lindgren, Karl-Oskar -- Liu, Tian -- Mangino, Massimo -- Marten, Jonathan -- Mihailov, Evelin -- Miller, Michael B -- van der Most, Peter J -- Oldmeadow, Christopher -- Payton, Antony -- Pervjakova, Natalia -- Peyrot, Wouter J -- Qian, Yong -- Raitakari, Olli -- Rueedi, Rico -- Salvi, Erika -- Schmidt, Borge -- Schraut, Katharina E -- Shi, Jianxin -- Smith, Albert V -- Poot, Raymond A -- St Pourcain, Beate -- Teumer, Alexander -- Thorleifsson, Gudmar -- Verweij, Niek -- Vuckovic, Dragana -- Wellmann, Juergen -- Westra, Harm-Jan -- Yang, Jingyun -- Zhao, Wei -- Zhu, Zhihong -- Alizadeh, Behrooz Z -- Amin, Najaf -- Bakshi, Andrew -- Baumeister, Sebastian E -- Biino, Ginevra -- Bonnelykke, Klaus -- Boyle, Patricia A -- Campbell, Harry -- Cappuccio, Francesco P -- Davies, Gail -- De Neve, Jan-Emmanuel -- Deloukas, Panos -- Demuth, Ilja -- Ding, Jun -- Eibich, Peter -- Eisele, Lewin -- Eklund, Niina -- Evans, David M -- Faul, Jessica D -- Feitosa, Mary F -- Forstner, Andreas J -- Gandin, Ilaria -- Gunnarsson, Bjarni -- Halldorsson, Bjarni V -- Harris, Tamara B -- Heath, Andrew C -- Hocking, Lynne J -- Holliday, Elizabeth G -- Homuth, Georg -- Horan, Michael A -- Hottenga, Jouke-Jan -- de Jager, Philip L -- Joshi, Peter K -- Jugessur, Astanand -- Kaakinen, Marika A -- Kahonen, Mika -- Kanoni, Stavroula -- Keltigangas-Jarvinen, Liisa -- Kiemeney, Lambertus A L M -- Kolcic, Ivana -- Koskinen, Seppo -- Kraja, Aldi T -- Kroh, Martin -- Kutalik, Zoltan -- Latvala, Antti -- Launer, Lenore J -- Lebreton, Mael P -- Levinson, Douglas F -- Lichtenstein, Paul -- Lichtner, Peter -- Liewald, David C M -- LifeLines Cohort Study -- Loukola, Anu -- Madden, Pamela A -- Magi, Reedik -- Maki-Opas, Tomi -- Marioni, Riccardo E -- Marques-Vidal, Pedro -- Meddens, Gerardus A -- McMahon, George -- Meisinger, Christa -- Meitinger, Thomas -- Milaneschi, Yusplitri -- Milani, Lili -- Montgomery, Grant W -- Myhre, Ronny -- Nelson, Christopher P -- Nyholt, Dale R -- Ollier, William E R -- Palotie, Aarno -- Paternoster, Lavinia -- Pedersen, Nancy L -- Petrovic, Katja E -- Porteous, David J -- Raikkonen, Katri -- Ring, Susan M -- Robino, Antonietta -- Rostapshova, Olga -- Rudan, Igor -- Rustichini, Aldo -- Salomaa, Veikko -- Sanders, Alan R -- Sarin, Antti-Pekka -- Schmidt, Helena -- Scott, Rodney J -- Smith, Blair H -- Smith, Jennifer A -- Staessen, Jan A -- Steinhagen-Thiessen, Elisabeth -- Strauch, Konstantin -- Terracciano, Antonio -- Tobin, Martin D -- Ulivi, Sheila -- Vaccargiu, Simona -- Quaye, Lydia -- van Rooij, Frank J A -- Venturini, Cristina -- Vinkhuyzen, Anna A E -- Volker, Uwe -- Volzke, Henry -- Vonk, Judith M -- Vozzi, Diego -- Waage, Johannes -- Ware, Erin B -- Willemsen, Gonneke -- Attia, John R -- Bennett, David A -- Berger, Klaus -- Bertram, Lars -- Bisgaard, Hans -- Boomsma, Dorret I -- Borecki, Ingrid B -- Bultmann, Ute -- Chabris, Christopher F -- Cucca, Francesco -- Cusi, Daniele -- Deary, Ian J -- Dedoussis, George V -- van Duijn, Cornelia M -- Eriksson, Johan G -- Franke, Barbara -- Franke, Lude -- Gasparini, Paolo -- Gejman, Pablo V -- Gieger, Christian -- Grabe, Hans-Jorgen -- Gratten, Jacob -- Groenen, Patrick J F -- Gudnason, Vilmundur -- van der Harst, Pim -- Hayward, Caroline -- Hinds, David A -- Hoffmann, Wolfgang -- Hypponen, Elina -- Iacono, William G -- Jacobsson, Bo -- Jarvelin, Marjo-Riitta -- Jockel, Karl-Heinz -- Kaprio, Jaakko -- Kardia, Sharon L R -- Lehtimaki, Terho -- Lehrer, Steven F -- Magnusson, Patrik K E -- Martin, Nicholas G -- McGue, Matt -- Metspalu, Andres -- Pendleton, Neil -- Penninx, Brenda W J H -- Perola, Markus -- Pirastu, Nicola -- Pirastu, Mario -- Polasek, Ozren -- Posthuma, Danielle -- Power, Christine -- Province, Michael A -- Samani, Nilesh J -- Schlessinger, David -- Schmidt, Reinhold -- Sorensen, Thorkild I A -- Spector, Tim D -- Stefansson, Kari -- Thorsteinsdottir, Unnur -- Thurik, A Roy -- Timpson, Nicholas J -- Tiemeier, Henning -- Tung, Joyce Y -- Uitterlinden, Andre G -- Vitart, Veronique -- Vollenweider, Peter -- Weir, David R -- Wilson, James F -- Wright, Alan F -- Conley, Dalton C -- Krueger, Robert F -- Davey Smith, George -- Hofman, Albert -- Laibson, David I -- Medland, Sarah E -- Meyer, Michelle N -- Yang, Jian -- Johannesson, Magnus -- Visscher, Peter M -- Esko, Tonu -- Koellinger, Philipp D -- Cesarini, David -- Benjamin, Daniel J -- P01-AG005842/AG/NIA NIH HHS/ -- P01-AG005842-20S2/AG/NIA NIH HHS/ -- P30-AG012810/AG/NIA NIH HHS/ -- R01-AG042568/AG/NIA NIH HHS/ -- T32-AG000186-23/AG/NIA NIH HHS/ -- England -- Nature. 2016 May 11;533(7604):539-42. doi: 10.1038/nature17671.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, 3062 PA, The Netherlands. ; Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, 3062 PA, The Netherlands. ; Department of Economics, Harvard University, Cambridge, Massachusetts 02138, USA. ; Center for Economic and Social Research, University of Southern California, Los Angeles, California 90089-3332, USA. ; Department of Psychology, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA. ; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 2116, USA. ; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen 2100, Denmark. ; Statens Serum Institut, Department of Epidemiology Research, Copenhagen 2300, Denmark. ; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. ; Icelandic Heart Association, Kopavogur 201, Iceland. ; Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik 107, Iceland. ; Department of Complex Trait Genetics, VU University, Center for Neurogenomics and Cognitive Research, Amsterdam, 1081 HV, The Netherlands. ; Amsterdam Business School, University of Amsterdam, Amsterdam, 1018 TV, The Netherlands. ; Department of Government, Uppsala University, Uppsala 751 20, Sweden. ; New York Genome Center, New York, New York 10013, USA. ; Department of Economics, New York University, New York, New York 10012, USA. ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark Lyngby 2800, Denmark. ; Department of Biological Psychology, VU University Amsterdam, Amsterdam, 1081 BT, The Netherlands. ; COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen 2820, Denmark. ; Steno Diabetes Center, Gentofte 2820, Denmark. ; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg 416 85, Sweden. ; Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; Institute of Epidemiology II, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; deCODE Genetics/Amgen Inc., Reykjavik 101, Iceland. ; Department of Cell Biology, Erasmus Medical Center Rotterdam, 3015 CN, The Netherlands. ; Istituto di Ricerca Genetica e Biomedica U.O.S. di Sassari, National Research Council of Italy, Sassari 07100, Italy. ; Psychology, University of Illinois, Champaign, Illinois 61820, USA. ; 23andMe, Inc., Mountain View, California 94041, USA. ; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands. ; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34100, Italy. ; Department of Public Health, University of Helsinki, 00014 Helsinki, Finland. ; Department of Cardiovascular Sciences, University of Leicester, Leicester LE3 9QP, UK. ; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK. ; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK. ; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Department of Neurology, General Hospital and Medical University Graz, Graz 8036, Austria. ; Institute for Medical Informatics, Statistics and Documentation, General Hospital and Medical University Graz, Graz 8036, Austria. ; Oxford Centre for Diabetes, Endocrinology &Metabolism, University of Oxford, Oxford OX3 7LE, UK. ; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK. ; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Institute of Behavioural Sciences, University of Helsinki, 00014 Helsinki, Finland. ; Nutrition and Dietetics, Health Science and Education, Harokopio University, Athens 17671, Greece. ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden. ; Folkhalsan Research Centre, 00014 Helsingfors, Finland. ; Institute for Computing and Information Sciences, Radboud University Nijmegen, Nijmegen, 6525 EC, The Netherlands. ; Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. ; Lifespan Psychology, Max Planck Institute for Human Development, Berlin 14195, Germany. ; Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK. ; NIHR Biomedical Research Centre, Guy's and St. Thomas' Foundation Trust, London SE1 7EH, UK. ; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia. ; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands. ; Public Health Stream, Hunter Medical Research Institute, New Lambton, NSW 2305, Australia. ; Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW 2300, Australia. ; Centre for Integrated Genomic Medical Research, Institute of Population Health, The University of Manchester, Manchester M13 9PT, UK. ; Human Communication and Deafness, School of Psychological Sciences, The University of Manchester, Manchester M13 9PL, UK. ; Department of Health, THL-National Institute for Health and Welfare, 00271 Helsinki, Finland. ; Psychiatry, VU University Medical Center &GGZ inGeest, Amsterdam, 1081 HL, The Netherlands. ; Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224, USA. ; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20521 Turku, Finland. ; Department of Medical Genetics, University of Lausanne, Lausanne 1005, Switzerland. ; Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland. ; Department Of Health Sciences, University of Milan, Milano 20142, Italy. ; Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen 45147, Germany. ; Centre for Global Health Research, The Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK. ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-9780, USA. ; Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland. ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK. ; School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, UK. ; Institute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands. ; Institute of Epidemiology and Social Medicine, University of Munster, Munster 48149, Germany. ; Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Partners Center for Personalized Genetic Medicine, Boston, Massachusetts 02115, USA. ; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois 60612, USA. ; Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. ; Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands. ; Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg D-93053, Germany. ; Institute of Molecular Genetics, National Research Council of Italy, Pavia 27100, Italy. ; Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. ; Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK. ; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK. ; Said Business School, University of Oxford, Oxford OX1 1HP, UK. ; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK. ; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia. ; The Berlin Aging Study II; Research Group on Geriatrics, Charite - Universitatsmedizin Berlin, Germany, Berlin 13347, Germany. ; Institute of Medical and Human Genetics, Charite-Universitatsmedizin, Berlin, Berlin 13353, Germany. ; German Socio- Economic Panel Study, DIW Berlin, Berlin 10117, Germany. ; Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK. ; The University of Queensland Diamantina Institute, The Translational Research Institute, Brisbane, QLD 4102, Australia. ; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63018, USA. ; Institute of Human Genetics, University of Bonn, Bonn 53127, Germany. ; Department of Genomics, Life and Brain Center, University of Bonn, Bonn 53127, Germany. ; Institute of Biomedical and Neural Engineering, School of Science and Engineering, Reykjavik University, Reykjavik 101, Iceland. ; Laboratory of Epidemiology, Demography, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892-9205, USA. ; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. ; Division of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK. ; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald 17475, Germany. ; Manchester Medical School, The University of Manchester, Manchester M13 9PT, UK. ; Program in Translational NeuroPsychiatric Genomics, Departments of Neurology &Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Genes and Environment, Norwegian Institute of Public Health, N-0403 Oslo, Norway. ; Department of Genomics of Common Disease, Imperial College London, London, W12 0NN, UK. ; Department of Clinical Physiology, Tampere University Hospital, 33521 Tampere, Finland. ; Department of Clinical Physiology, University of Tampere, School of Medicine, 33014 Tampere, Finland. ; Public Health, Medical School, University of Split, 21000 Split, Croatia. ; Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne 1010, Switzerland. ; Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892-9205, USA. ; Amsterdam Brain and Cognition Center, University of Amsterdam, Amsterdam, 1018 XA, The Netherlands. ; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305-5797, USA. ; Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. ; Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne 1011, Switzerland. ; Tema BV, Hoofddorp, 2131 HE, The Netherlands. ; Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. ; Institute of Health and Biomedical Innovation, Queensland Institute of Technology, Brisbane, QLD 4059, Australia. ; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. ; Psychiatric &Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00014, Finland. ; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ; Medical Genetics, Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste 34100, Italy. ; Social Impact, Arlington, Virginia 22201, USA. ; Department of Economics, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, USA. ; Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, Illinois 60201-3137, USA. ; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois 60637, USA. ; Public Health Genomics Unit, National Institute for Health and Welfare, 00300 Helsinki, Finland. ; Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University, Graz, Graz 8010, Austria. ; Information Based Medicine Stream, Hunter Medical Research Institute, New Lambton, NSW 2305, Australia. ; Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK. ; Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Science, University of Leuven, Leuven 3000, Belgium. ; R&D VitaK Group, Maastricht University, Maastricht, 6229 EV, The Netherlands. ; Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg 85764, Germany. ; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig Maximilians-Universitat, Munich 81377, Germany. ; Department of Geriatrics, Florida State University College of Medicine, Tallahassee, Florida 32306, USA. ; Department of Health Sciences and Genetics, University of Leicester, Leicester LE1 7RH, UK. ; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Research Center for Group Dynamics, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48104, USA. ; Platform for Genome Analytics, Institutes of Neurogenetics &Integrative and Experimental Genomics, University of Lubeck, Lubeck 23562, Germany. ; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK. ; Department of Health Sciences, Community &Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, 9713 AV, The Netherlands. ; Department of Psychology, Union College, Schenectady, New York 12308, USA. ; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 9042, Italy. ; Institute of Biomedical Technologies, Italian National Research Council, Segrate (Milano) 20090, Italy. ; Department of General Practice and Primary Health Care, University of Helsinki, 00014 Helsinki, Finland. ; Departments of Human Genetics and Psychiatry, Donders Centre for Neuroscience, Nijmegen, 6500 HB, The Netherlands. ; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands. ; Sidra, Experimental Genetics Division, Sidra, Doha 26999, Qatar. ; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald 17475, Germany. ; Department of Psychiatry and Psychotherapy, HELIOS-Hospital Stralsund, Stralsund 18437, Germany. ; Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, 3062 PA, The Netherlands. ; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, 1105 AZ, The Netherlands. ; Generation Scotland, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. ; Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia. ; South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia. ; Population, Policy and Practice, UCL Institute of Child Health, London WC1N 1EH, UK. ; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment &Health, School of Public Health, Imperial College London, London W2 1PG, UK. ; Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, 90014 Oulu, Finland. ; Unit of Primary Care, Oulu University Hospital, 90029 Oulu, Finland. ; Biocenter Oulu, University of Oulu, 90014 Oulu, Finland. ; Fimlab Laboratories, 33520 Tampere, Finland. ; Department of Clinical Chemistry, University of Tampere, School of Medicine, 33014 Tampere, Finland. ; Economics, NYU Shanghai, 200122 Pudong, China. ; Policy Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada. ; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. ; Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia. ; Centre for Clinical and Cognitive Neuroscience, Institute Brain Behaviour and Mental Health, Salford Royal Hospital, Manchester M6 8HD, UK. ; Manchester Institute for Collaborative Research in Ageing, University of Manchester, Manchester M13 9PL, UK. ; Faculty of Medicine, University of Split, Split 21000, Croatia. ; Department of Clinical Genetics, VU Medical Centre, Amsterdam, 1081 HV, The Netherlands. ; Institute of Preventive Medicine. Bispebjerg and Frederiksberg Hospitals, The Capital Region, Frederiksberg 2000, Denmark. ; Montpellier Business School, Montpellier 34080, France. ; Panteia, Zoetermeer, 2715 CA, The Netherlands. ; Department of Psychiatry, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands. ; Department of Sociology, New York University, New York, New York 10012, USA. ; School of Medicine, New York University, New York, New York 10016, USA. ; Bioethics Program, Union Graduate College - Icahn School of Medicine at Mount Sinai, Schenectady, New York 12308, USA. ; Department of Economics, Stockholm School of Economics, Stockholm 113 83, Sweden. ; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Research Institute for Industrial Economics, Stockholm 10215, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27225129" target="_blank"〉PubMed〈/a〉

Description: Roughly one in three individuals is highly susceptible to motion sickness and yet the underlying causes of this condition are not well understood. Despite high heritability, no associated genetic factors have been discovered. Here, we conducted the first genome-wide association study on motion sickness in 80 494 individuals from the 23andMe database who were surveyed about car sickness. Thirty-five single-nucleotide polymorphisms (SNPs) were associated with motion sickness at a genome-wide-significant level ( P 〈 5 x 10 –8 ). Many of these SNPs are near genes involved in balance, and eye, ear and cranial development (e.g. PVRL3, TSHZ1, MUTED, HOXB3, HOXD3). Other SNPs may affect motion sickness through nearby genes with roles in the nervous system, glucose homeostasis or hypoxia. We show that several of these SNPs display sex-specific effects, with up to three times stronger effects in women. We searched for comorbid phenotypes with motion sickness, confirming associations with known comorbidities including migraines, postoperative nausea and vomiting (PONV), vertigo and morning sickness and observing new associations with altitude sickness and many gastrointestinal conditions. We also show that two of these related phenotypes (PONV and migraines) share underlying genetic factors with motion sickness. These results point to the importance of the nervous system in motion sickness and suggest a role for glucose levels in motion-induced nausea and vomiting, a finding that may provide insight into other nausea-related phenotypes like PONV. They also highlight personal characteristics (e.g. being a poor sleeper) that correlate with motion sickness, findings that could help identify risk factors or treatments.

Description: Thrombotic diseases are among the leading causes of morbidity and mortality in the world. To add insights into the genetic regulation of thrombotic disease, we conducted a genome-wide association study (GWAS) of 6135 self-reported blood clots events and 252 827 controls of European ancestry belonging to the 23andMe cohort of research participants. Eight loci exceeded genome-wide significance. Among the genome-wide significant results, our study replicated previously known venous thromboembolism (VTE) loci near the F5, FGA-FGG, F11, F2, PROCR and ABO genes, and the more recently discovered locus near SLC44A2 . In addition, our study reports for the first time a genome-wide significant association between rs114209171, located upstream of the F8 structural gene, and thrombosis risk. Analyses of expression profiles and expression quantitative trait loci across different tissues suggested SLC44A2 , ILF3 and AP1M2 as the three most plausible candidate genes for the chromosome 19 locus, our only genome-wide significant thrombosis-related locus that does not harbor likely coagulation-related genes. In addition, we present data showing that this locus also acts as a novel risk factor for stroke and coronary artery disease (CAD). In conclusion, our study reveals novel common genetic risk factors for VTE, stroke and CAD and provides evidence that self-reported data on blood clots used in a GWAS yield results that are comparable with those obtained using clinically diagnosed VTE. This observation opens up the potential for larger meta-analyses, which will enable elucidation of the genetics of thrombotic diseases, and serves as an example for the genetic study of other diseases.