%0 Journal Article %J Molecular Psychiatry %D 2022 %T Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning. %A Lahti, Jari %A Tuominen, Samuli %A Yang, Qiong %A Pergola, Giulio %A Ahmad, Shahzad %A Amin, Najaf %A Armstrong, Nicola J %A Beiser, Alexa %A Bey, Katharina %A Bis, Joshua C %A Boerwinkle, Eric %A Bressler, Jan %A Campbell, Archie %A Campbell, Harry %A Chen, Qiang %A Corley, Janie %A Cox, Simon R %A Davies, Gail %A De Jager, Philip L %A Derks, Eske M %A Jessica Faul %A Fitzpatrick, Annette L %A Fohner, Alison E %A Ford, Ian %A Fornage, Myriam %A Gerring, Zachary %A Grabe, Hans J %A Grodstein, Francine %A Gudnason, Vilmundur %A Simonsick, Eleanor %A Holliday, Elizabeth G %A Joshi, Peter K %A Kajantie, Eero %A Kaprio, Jaakko %A Karell, Pauliina %A Kleineidam, Luca %A Knol, Maria J %A Kochan, Nicole A %A Kwok, John B %A Leber, Markus %A Lam, Max %A Lee, Teresa %A Li, Shuo %A Loukola, Anu %A Luck, Tobias %A Marioni, Riccardo E %A Mather, Karen A %A Medland, Sarah %A Mirza, Saira S %A Nalls, Mike A %A Nho, Kwangsik %A O'Donnell, Adrienne %A Oldmeadow, Christopher %A Painter, Jodie %A Pattie, Alison %A Reppermund, Simone %A Risacher, Shannon L %A Rose, Richard J %A Sadashivaiah, Vijay %A Scholz, Markus %A Satizabal, Claudia L %A Schofield, Peter W %A Schraut, Katharina E %A Scott, Rodney J %A Simino, Jeannette %A Smith, Albert V %A Smith, Jennifer A %A Stott, David J %A Surakka, Ida %A Teumer, Alexander %A Thalamuthu, Anbupalam %A Trompet, Stella %A Turner, Stephen T %A van der Lee, Sven J %A Villringer, Arno %A Völker, Uwe %A Wilson, Robert S %A Wittfeld, Katharina %A Vuoksimaa, Eero %A Xia, Rui %A Yaffe, Kristine %A Yu, Lei %A Zare, Habil %A Zhao, Wei %A Ames, David %A Attia, John %A Bennett, David A %A Brodaty, Henry %A Chasman, Daniel I %A Goldman, Aaron L %A Hayward, Caroline %A Ikram, M Arfan %A Jukema, J Wouter %A Sharon L R Kardia %A Lencz, Todd %A Loeffler, Markus %A Mattay, Venkata S %A Palotie, Aarno %A Psaty, Bruce M %A Ramirez, Alfredo %A Ridker, Paul M %A Riedel-Heller, Steffi G %A Sachdev, Perminder S %A Saykin, Andrew J %A Scherer, Martin %A Schofield, Peter R %A Sidney, Stephen %A Starr, John M %A Trollor, Julian %A Ulrich, William %A Wagner, Michael %A David R Weir %A Wilson, James F %A Wright, Margaret J %A Weinberger, Daniel R %A Debette, Stéphanie %A Eriksson, Johan G %A Mosley, Thomas H %A Launer, Lenore J %A van Duijn, Cornelia M %A Deary, Ian J %A Seshadri, Sudha %A Räikkönen, Katri %K Genome %K health outcomes %K Memory %K neurocognitive outcomes %K polygenic score %K Verbal Learning %X
Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
%B Molecular Psychiatry %G eng %R 10.1038/s41380-022-01710-8 %0 Journal Article %J Nature Human Behaviour %D 2019 %T New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders. %A Evangelou, Evangelos %A Gao, He %A Chu, Congying %A Ntritsos, Georgios %A Blakeley, Paul %A Butts, Andrew R %A Pazoki, Raha %A Suzuki, Hideaki %A Koskeridis, Fotios %A Yiorkas, Andrianos M %A Karaman, Ibrahim %A Elliott, Joshua %A Luo, Qiang %A Aeschbacher, Stefanie %A Traci M Bartz %A Baumeister, Sebastian E %A Braund, Peter S %A Brown, Michael R %A Brody, Jennifer A %A Clarke, Toni-Kim %A Dimou, Niki %A Jessica Faul %A Homuth, Georg %A Jackson, Anne U %A Kentistou, Katherine A %A Joshi, Peter K %A Lemaitre, Rozenn N %A Penelope A Lind %A Lyytikäinen, Leo-Pekka %A Mangino, Massimo %A Milaneschi, Yuri %A Nelson, Christopher P %A Ilja M Nolte %A Perälä, Mia-Maria %A Polasek, Ozren %A David J Porteous %A Scott M Ratliff %A Smith, Jennifer A %A Stančáková, Alena %A Teumer, Alexander %A Tuominen, Samuli %A Thériault, Sébastien %A Vangipurapu, Jagadish %A Whitfield, John B %A Wood, Alexis %A Yao, Jie %A Yu, Bing %A Zhao, Wei %A Dan E Arking %A Auvinen, Juha %A Liu, Chunyu %A Männikkö, Minna %A Risch, Lorenz %A Rotter, Jerome I %A Snieder, Harold %A Veijola, Juha %A Alexandra I Blakemore %A Boehnke, Michael %A Campbell, Harry %A Conen, David %A Johan G Eriksson %A Hans-Jörgen Grabe %A Guo, Xiuqing %A van der Harst, Pim %A Catharina A Hartman %A Caroline Hayward %A Andrew C Heath %A Järvelin, Marjo-Riitta %A Kähönen, Mika %A Sharon L R Kardia %A Kühne, Michael %A Kuusisto, Johanna %A Laakso, Markku %A Lahti, Jari %A Lehtimäki, Terho %A McIntosh, Andrew M %A Mohlke, Karen L %A Alanna C Morrison %A Nicholas G Martin %A Oldehinkel, Albertine J %A Brenda W J H Penninx %A Psaty, Bruce M %A Olli T Raitakari %A Rudan, Igor %A Nilesh J Samani %A Scott, Laura J %A Timothy Spector %A Verweij, Niek %A David R Weir %A James F Wilson %A Levy, Daniel %A Tzoulaki, Ioanna %A Bell, Jimmy D %A Matthews, Paul M %A Rothenfluh, Adrian %A Desrivières, Sylvane %A Schumann, Gunter %A Elliott, Paul %K Adult %K Aged %K Alcohol Drinking %K Alcoholism %K Brain %K Female %K genes %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Humans %K Magnetic Resonance Imaging %K Male %K Mental Disorders %K Middle Aged %K Neuroimaging %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Schizophrenia %K Whites %XExcessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.
%B Nature Human Behaviour %V 3 %P 950-961 %G eng %N 9 %R 10.1038/s41562-019-0653-z %0 Journal Article %J Nature Genetics %D 2018 %T Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. %A Lee, James J %A Wedow, Robbee %A Okbay, Aysu %A Kong, Edward %A Maghzian, Omeed %A Zacher, Meghan %A Nguyen-Viet, Tuan Anh %A Bowers, Peter %A Sidorenko, Julia %A Richard Karlsson Linnér %A Mark Alan Fontana %A Kundu, Tushar %A Lee, Chanwook %A Hui Liu %A Li, Ruoxi %A Royer, Rebecca %A Pascal N Timshel %A Walters, Raymond K %A Willoughby, Emily A %A Yengo, Loic %A Alver, Maris %A Bao, Yanchun %A Clark, David W %A Day, Felix R %A Furlotte, Nicholas A %A Joshi, Peter K %A Kathryn E Kemper %A Kleinman, Aaron %A Langenberg, Claudia %A Mägi, Reedik %A Joey W Trampush %A Verma, Shefali Setia %A Wu, Yang %A Lam, Max %A Jing Hua Zhao %A Zheng, Zhili %A Jason D Boardman %A Campbell, Harry %A Freese, Jeremy %A Kathleen Mullan Harris %A Caroline Hayward %A Herd, Pamela %A Kumari, Meena %A Lencz, Todd %A Luan, Jian'an %A Anil K. Malhotra %A Andres Metspalu %A Lili Milani %A Ong, Ken K %A Perry, John R B %A David J Porteous %A Ritchie, Marylyn D %A Smart, Melissa C %A Smith, Blair H %A Tung, Joyce Y %A Wareham, Nicholas J %A James F Wilson %A Jonathan P. Beauchamp %A Dalton C Conley %A Tõnu Esko %A Lehrer, Steven F %A Patrik K E Magnusson %A Oskarsson, Sven %A Pers, Tune H %A Matthew R Robinson %A Thom, Kevin %A Watson, Chelsea %A Chabris, Christopher F %A Meyer, Michelle N %A David I Laibson %A Yang, Jian %A Johannesson, Magnus %A Philipp D Koellinger %A Turley, Patrick %A Peter M Visscher %A Daniel J. Benjamin %A Cesarini, David %K Adult %K Aged %K Aged, 80 and over %K Cohort Studies %K Educational Status %K Female %K Genome-Wide Association Study %K Humans %K Male %K Middle Aged %K Multifactorial Inheritance %K Phenotype %K Polymorphism, Single Nucleotide %XHere we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
%B Nature Genetics %V 50 %P 1112-1121 %8 2018 07 23 %G eng %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/30038396?dopt=Abstract %R 10.1038/s41588-018-0147-3 %0 Journal Article %J Nature Communications %D 2018 %T Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. %A Gail Davies %A Lam, Max %A Sarah E Harris %A Joey W Trampush %A Luciano, Michelle %A W David Hill %A Hagenaars, Saskia P %A Ritchie, Stuart J %A Riccardo E Marioni %A Fawns-Ritchie, Chloe %A David C Liewald %A Okely, Judith A %A Ahola-Olli, Ari V %A Barnes, Catriona L K %A Bertram, Lars %A Joshua C. Bis %A Katherine E Burdick %A Christoforou, Andrea %A DeRosse, Pamela %A Djurovic, Srdjan %A Espeseth, Thomas %A Giakoumaki, Stella %A Giddaluru, Sudheer %A Gustavson, Daniel E %A Caroline Hayward %A Edith Hofer %A Ikram, M Arfan %A Karlsson, Robert %A Knowles, Emma %A Lahti, Jari %A Leber, Markus %A Li, Shuo %A Mather, Karen A %A Melle, Ingrid %A Morris, Derek %A Christopher J Oldmeadow %A Palviainen, Teemu %A Payton, Antony %A Pazoki, Raha %A Katja E Petrovic %A Chandra A Reynolds %A Sargurupremraj, Muralidharan %A Scholz, Markus %A Smith, Jennifer A %A Smith, Albert V %A Terzikhan, Natalie %A Thalamuthu, Anbupalam %A Trompet, Stella %A Sven J van der Lee %A Erin B Ware %A Windham, B Gwen %A Margaret J Wright %A Yang, Jingyun %A Yu, Jin %A Ames, David %A Amin, Najaf %A Amouyel, Philippe %A Andreassen, Ole A %A Armstrong, Nicola J %A Assareh, Amelia A %A John R. Attia %A Attix, Deborah %A Avramopoulos, Dimitrios %A David A Bennett %A Böhmer, Anne C %A Patricia A. Boyle %A Brodaty, Henry %A Campbell, Harry %A Tyrone D. Cannon %A Elizabeth T. Cirulli %A Congdon, Eliza %A Conley, Emily Drabant %A Corley, Janie %A Cox, Simon R %A Dale, Anders M %A Dehghan, Abbas %A Danielle M. Dick %A Dickinson, Dwight %A Johan G Eriksson %A Evangelou, Evangelos %A Jessica Faul %A Ford, Ian %A Nelson A. Freimer %A Gao, He %A Giegling, Ina %A Gillespie, Nathan A %A Gordon, Scott D %A Gottesman, Rebecca F %A Michael E Griswold %A Gudnason, Vilmundur %A Tamara B Harris %A Hartmann, Annette M %A Hatzimanolis, Alex %A Gerardo Heiss %A Holliday, Elizabeth G %A Joshi, Peter K %A Kähönen, Mika %A Sharon L R Kardia %A Ida Karlsson %A Kleineidam, Luca %A David S Knopman %A Kochan, Nicole A %A Konte, Bettina %A Kwok, John B %A Stephanie Le Hellard %A Lee, Teresa %A Lehtimäki, Terho %A Li, Shu-Chen %A Lill, Christina M %A Liu, Tian %A Koini, Marisa %A London, Edythe %A Longstreth, Will T %A Lopez, Oscar L %A Loukola, Anu %A Luck, Tobias %A Astri J Lundervold %A Lundquist, Anders %A Lyytikäinen, Leo-Pekka %A Nicholas G Martin %A Grant W Montgomery %A Murray, Alison D %A Anna C Need %A Noordam, Raymond %A Nyberg, Lars %A William E R Ollier %A Papenberg, Goran %A Pattie, Alison %A Polasek, Ozren %A Russell A Poldrack %A Psaty, Bruce M %A Reppermund, Simone %A Steffi G Riedel-Heller %A Rose, Richard J %A Rotter, Jerome I %A Roussos, Panos %A Rovio, Suvi P %A Saba, Yasaman %A Fred W Sabb %A Sachdev, Perminder S %A Satizabal, Claudia L %A Schmid, Matthias %A Rodney J Scott %A Matthew A Scult %A Simino, Jeannette %A Slagboom, P Eline %A Smyrnis, Nikolaos %A Soumaré, Aïcha %A Nikos C Stefanis %A Stott, David J %A Richard E Straub %A Sundet, Kjetil %A Taylor, Adele M %A Kent D Taylor %A Tzoulaki, Ioanna %A Tzourio, Christophe %A André G Uitterlinden %A Vitart, Veronique %A Aristotle N Voineskos %A Kaprio, Jaakko %A Wagner, Michael %A Wagner, Holger %A Weinhold, Leonie %A Wen, K Hoyan %A Elisabeth Widen %A Yang, Qiong %A Zhao, Wei %A Hieab H Adams %A Dan E Arking %A Robert M Bilder %A Bitsios, Panos %A Boerwinkle, Eric %A Chiba-Falek, Ornit %A Corvin, Aiden %A Philip L de Jager %A Debette, Stéphanie %A Donohoe, Gary %A Elliott, Paul %A Fitzpatrick, Annette L %A Gill, Michael %A David C. Glahn %A Hägg, Sara %A Narelle K Hansell %A Ahmad R Hariri %A Ikram, M Kamran %A Jukema, J Wouter %A Vuoksimaa, Eero %A Matthew C Keller %A Kremen, William S %A Lenore J Launer %A Lindenberger, Ulman %A Aarno Palotie %A Nancy L Pedersen %A Pendleton, Neil %A David J Porteous %A Katri Räikkönen %A Olli T Raitakari %A Ramirez, Alfredo %A Reinvang, Ivar %A Rudan, Igor %A Schmidt, Reinhold %A Schmidt, Helena %A Peter W Schofield %A Peter R Schofield %A John M Starr %A Vidar M Steen %A Trollor, Julian N %A Turner, Steven T %A Cornelia M van Duijn %A Villringer, Arno %A Daniel R Weinberger %A David R Weir %A James F Wilson %A Anil K. Malhotra %A McIntosh, Andrew M %A Gale, Catharine R %A Seshadri, Sudha %A Thomas H Mosley %A Bressler, Jan %A Lencz, Todd %A Ian J Deary %K Adolescent %K Adult %K Aged %K Aged, 80 and over %K Cognition %K Genetic Loci %K Genetic Predisposition to Disease %K Humans %K Mental Disorders %K Middle Aged %K Multifactorial Inheritance %K Neurodegenerative Diseases %K Neurodevelopmental Disorders %K Polymorphism, Single Nucleotide %K Reaction Time %K Young Adult %XGeneral cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
%B Nature Communications %V 9 %P 2098 %G eng %N 1 %R 10.1038/s41467-018-04362-x %0 Journal Article %J Nature Communications %D 2017 %T Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. %A Joshi, Peter K %A Nicola Pirastu %A Kentistou, Katherine A %A Fischer, Krista %A Edith Hofer %A Schraut, Katharina E %A Clark, David W %A Nutile, Teresa %A Barnes, Catriona L K %A Paul Rhj Timmers %A Shen, Xia %A Gandin, Ilaria %A McDaid, Aaron F %A Hansen, Thomas Folkmann %A Gordon, Scott D %A Giulianini, Franco %A Boutin, Thibaud S %A Abdellaoui, Abdel %A Zhao, Wei %A Medina-Gomez, Carolina %A Traci M Bartz %A Trompet, Stella %A Leslie A Lange %A Raffield, Laura %A van der Spek, Ashley %A Galesloot, Tessel E %A Proitsi, Petroula %A Yanek, Lisa R %A Bielak, Lawrence F %A Payton, Antony %A Murgia, Federico %A Concas, Maria Pina %A Biino, Ginevra %A Tajuddin, Salman M %A Seppälä, Ilkka %A Amin, Najaf %A Boerwinkle, Eric %A Børglum, Anders D %A Campbell, Archie %A Ellen W Demerath %A Demuth, Ilja %A Jessica Faul %A Ford, Ian %A Gialluisi, Alessandro %A Gögele, Martin %A Graff, Mariaelisa %A Aroon Hingorani %A Jouke-Jan Hottenga %A Hougaard, David M %A Hurme, Mikko A %A Ikram, M Arfan %A Jylhä, Marja %A Kuh, Diana %A Ligthart, Lannie %A Lill, Christina M %A Lindenberger, Ulman %A Lumley, Thomas %A Mägi, Reedik %A Marques-Vidal, Pedro %A Sarah E Medland %A Lili Milani %A Nagy, Reka %A William E R Ollier %A Peyser, Patricia A %A Pramstaller, Peter P %A Ridker, Paul M %A Fernando Rivadeneira %A Ruggiero, Daniela %A Saba, Yasaman %A Schmidt, Reinhold %A Schmidt, Helena %A Slagboom, P Eline %A Smith, Blair H %A Smith, Jennifer A %A Sotoodehnia, Nona %A Steinhagen-Thiessen, Elisabeth %A van Rooij, Frank J A %A Verbeek, André L %A Vermeulen, Sita H %A Vollenweider, Peter %A Wang, Yunpeng %A Werge, Thomas %A Whitfield, John B %A Alan B Zonderman %A Lehtimäki, Terho %A Michele K Evans %A Pirastu, Mario %A Fuchsberger, Christian %A Bertram, Lars %A Pendleton, Neil %A Sharon L R Kardia %A Ciullo, Marina %A Becker, Diane M %A Wong, Andrew %A Psaty, Bruce M %A Cornelia M van Duijn %A Wilson, James G %A Jukema, J Wouter %A Lambertus A Kiemeney %A André G Uitterlinden %A Franceschini, Nora %A Kari E North %A David R Weir %A Andres Metspalu %A Dorret I Boomsma %A Caroline Hayward %A Daniel I Chasman %A Nicholas G Martin %A Sattar, Naveed %A Campbell, Harry %A Tõnu Esko %A Kutalik, Zoltán %A James F Wilson %K Alleles %K Body Mass Index %K Coronary Disease %K Education %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K HLA-DQ alpha-Chains %K HLA-DRB1 Chains %K Humans %K Insulin Resistance %K Life Style %K Lipoprotein(a) %K Lipoproteins, HDL %K Longevity %K Lung Neoplasms %K Obesity %K Polymorphism, Single Nucleotide %K Smoking %K Socioeconomic factors %XGenomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.
%B Nature Communications %V 8 %P 910 %G eng %N 1 %R 10.1038/s41467-017-00934-5 %0 Journal Article %J Nat Genet %D 2016 %T Genome-wide analysis identifies 12 loci influencing human reproductive behavior. %A Nicola Barban %A Jansen, Rick %A de Vlaming, Ronald %A Vaez, Ahmad %A Mandemakers, Jornt J %A Felix C Tropf %A Shen, Xia %A James F Wilson %A Daniel I Chasman %A Ilja M Nolte %A Tragante, Vinicius %A van der Laan, Sander W %A Perry, John R B %A Kong, Augustine %A Ahluwalia, Tarunveer S %A Albrecht, Eva %A Laura M Yerges-Armstrong %A Atzmon, Gil %A Auro, Kirsi %A Kristin L. Ayers %A Bakshi, Andrew %A Ben-Avraham, Danny %A Klaus Berger %A Bergman, Aviv %A Bertram, Lars %A Bielak, Lawrence F %A Bjornsdottir, Gyda %A Bonder, Marc Jan %A Broer, Linda %A Bui, Minh %A Barbieri, Caterina %A Cavadino, Alana %A Chavarro, Jorge E %A Turman, Constance %A Maria Pina Concas %A Cordell, Heather J %A Gail Davies %A Eibich, Peter %A Eriksson, Nicholas %A Tõnu Esko %A Eriksson, Joel %A Falahi, Fahimeh %A Felix, Janine F %A Mark Alan Fontana %A Lude L Franke %A Gandin, Ilaria %A Gaskins, Audrey J %A Gieger, Christian %A Gunderson, Erica P %A Guo, Xiuqing %A Caroline Hayward %A He, Chunyan %A Edith Hofer %A Huang, Hongyan %A Joshi, Peter K %A Kanoni, Stavroula %A Karlsson, Robert %A Kiechl, Stefan %A Kifley, Annette %A Kluttig, Alexander %A Kraft, Peter %A Lagou, Vasiliki %A Lecoeur, Cecile %A Lahti, Jari %A Li-Gao, Ruifang %A Penelope A Lind %A Tian Liu %A Makalic, Enes %A Mamasoula, Crysovalanto %A Lindsay K Matteson %A Mbarek, Hamdi %A McArdle, Patrick F %A McMahon, George %A Meddens, S Fleur W %A Mihailov, Evelin %A Michael B Miller %A Missmer, Stacey A %A Monnereau, Claire %A van der Most, Peter J %A Myhre, Ronny %A Michael A Nalls %A Nutile, Teresa %A Ioanna Panagiota Kalafati %A Porcu, Eleonora %A Prokopenko, Inga %A Rajan, Kumar B %A Rich-Edwards, Janet %A Cornelius A Rietveld %A Robino, Antonietta %A Rose, Lynda M %A Rueedi, Rico %A Ryan, Kathleen A %A Saba, Yasaman %A Schmidt, Daniel %A Jennifer A Smith %A Stolk, Lisette %A Streeten, Elizabeth %A Tönjes, Anke %A Thorleifsson, Gudmar %A Ulivi, Sheila %A Wedenoja, Juho %A Jürgen Wellmann %A Willeit, Peter %A Yao, Jie %A Yengo, Loic %A Jing Hua Zhao %A Wei Zhao %A Zhernakova, Daria V %A Amin, Najaf %A Andrews, Howard %A Balkau, Beverley %A Barzilai, Nir %A Bergmann, Sven %A Biino, Ginevra %A Bisgaard, Hans %A Bønnelykke, Klaus %A Dorret I Boomsma %A Buring, Julie E %A Campbell, Harry %A Cappellani, Stefania %A Ciullo, Marina %A Cox, Simon R %A Francesco Cucca %A Toniolo, Daniela %A Davey-Smith, George %A Ian J Deary %A George Dedoussis %A Deloukas, Panos %A Cornelia M van Duijn %A Eco J. C. de Geus %A Johan G Eriksson %A Jessica Faul %A Cinzia Felicita Sala %A Froguel, Philippe %A Paolo P. Gasparini %A Giorgia G Girotto %A Hans-Jörgen Grabe %A Greiser, Karin Halina %A Groenen, Patrick J F %A de Haan, Hugoline G %A Haerting, Johannes %A Tamara B Harris %A Andrew C Heath %A Heikkilä, Kauko %A Hofman, Albert %A Homuth, Georg %A Holliday, Elizabeth G %A John L Hopper %A Hyppönen, Elina %A Jacobsson, Bo %A Vincent Jaddoe %A Johannesson, Magnus %A Jugessur, Astanand %A Kähönen, Mika %A Kajantie, Eero %A Sharon L R Kardia %A Keavney, Bernard %A Kolcic, Ivana %A Koponen, Päivikki %A Kovacs, Peter %A Kronenberg, Florian %A Kutalik, Zoltán %A La Bianca, Martina %A Lachance, Genevieve %A Iacono, William G %A Lai, Sandra %A Lehtimäki, Terho %A David C Liewald %A Lindgren, Cecilia M %A Yongmei Liu %A Luben, Robert %A Lucht, Michael %A Luoto, Riitta %A Magnus, Per %A Patrik K E Magnusson %A Nicholas G Martin %A McGue, Matt %A McQuillan, Ruth %A Sarah E Medland %A Meisinger, Christa %A Mellström, Dan %A Andres Metspalu %A Traglia, Michela %A Lili Milani %A Mitchell, Paul %A Grant W Montgomery %A Dennis O Mook-Kanamori %A de Mutsert, Renée %A Nohr, Ellen A %A Ohlsson, Claes %A Olsen, Jørn %A Ong, Ken K %A Paternoster, Lavinia %A Pattie, Alison %A Brenda W J H Penninx %A Markus Perola %A Peyser, Patricia A %A Pirastu, Mario %A Polasek, Ozren %A Power, Chris %A Kaprio, Jaakko %A Raffel, Leslie J %A Katri Räikkönen %A Olli T Raitakari %A Ridker, Paul M %A Ring, Susan M %A Roll, Kathryn %A Rudan, Igor %A Ruggiero, Daniela %A Rujescu, Dan %A Veikko Salomaa %A Schlessinger, David %A Schmidt, Helena %A Schmidt, Reinhold %A Schupf, Nicole %A Johannes H Smit %A Sorice, Rossella %A Timothy Spector %A John M Starr %A Stöckl, Doris %A Strauch, Konstantin %A Stumvoll, Michael %A Swertz, Morris A %A Thorsteinsdottir, Unnur %A A. Roy Thurik %A Nicholas J Timpson %A Tung, Joyce Y %A André G Uitterlinden %A Vaccargiu, Simona %A Viikari, Jorma %A Vitart, Veronique %A Völzke, Henry %A Vollenweider, Peter %A Vuckovic, Dragana %A Waage, Johannes %A Wagner, Gert G %A Wang, Jie Jin %A Wareham, Nicholas J %A David R Weir %A Gonneke Willemsen %A Willeit, Johann %A Alan F Wright %A Krina T Zondervan %A Stefansson, Kari %A Krueger, Robert F %A Lee, James J %A Daniel J. Benjamin %A Cesarini, David %A Philipp D Koellinger %A den Hoed, Marcel %A Snieder, Harold %A Melinda C Mills %XThe genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.
%B Nat Genet %V 48 %P 1462-1472 %8 2016 Dec %G eng %N 12 %1 http://www.ncbi.nlm.nih.gov/pubmed/27798627?dopt=Abstract %R 10.1038/ng.3698 %0 Journal Article %J Nature %D 2016 %T Genome-wide association study identifies 74 loci associated with educational attainment. %A Okbay, Aysu %A Jonathan P. Beauchamp %A Mark Alan Fontana %A Lee, James J %A Pers, Tune H %A Cornelius A Rietveld %A Turley, Patrick %A Chen, Guo-Bo %A Emilsson, Valur %A Meddens, S Fleur W %A Oskarsson, Sven %A Pickrell, Joseph K %A Thom, Kevin %A Pascal N Timshel %A de Vlaming, Ronald %A Abdel Abdellaoui %A Ahluwalia, Tarunveer S %A Bacelis, Jonas %A Baumbach, Clemens %A Bjornsdottir, Gyda %A Brandsma, Johannes H %A Maria Pina Concas %A Derringer, Jaime %A Furlotte, Nicholas A %A Galesloot, Tessel E %A Giorgia G Girotto %A Gupta, Richa %A Hall, Leanne M %A Sarah E Harris %A Edith Hofer %A Horikoshi, Momoko %A Huffman, Jennifer E %A Kaasik, Kadri %A Ioanna Panagiota Kalafati %A Karlsson, Robert %A Kong, Augustine %A Lahti, Jari %A Sven J van der Lee %A Christiaan de Leeuw %A Penelope A Lind %A Lindgren, Karl-Oskar %A Tian Liu %A Mangino, Massimo %A Marten, Jonathan %A Mihailov, Evelin %A Michael B Miller %A van der Most, Peter J %A Christopher J Oldmeadow %A Payton, Antony %A Pervjakova, Natalia %A Wouter J Peyrot %A Qian, Yong %A Olli T Raitakari %A Rueedi, Rico %A Salvi, Erika %A Schmidt, Börge %A Schraut, Katharina E %A Jianxin Shi %A Albert Vernon Smith %A Poot, Raymond A %A St Pourcain, Beate %A Teumer, Alexander %A Thorleifsson, Gudmar %A Verweij, Niek %A Vuckovic, Dragana %A Jürgen Wellmann %A Westra, Harm-Jan %A Yang, Jingyun %A Wei Zhao %A Zhihong Zhu %A Alizadeh, Behrooz Z %A Amin, Najaf %A Bakshi, Andrew %A Baumeister, Sebastian E %A Biino, Ginevra %A Bønnelykke, Klaus %A Patricia A. Boyle %A Campbell, Harry %A Cappuccio, Francesco P %A Gail Davies %A De Neve, Jan-Emmanuel %A Deloukas, Panos %A Demuth, Ilja %A Ding, Jun %A Eibich, Peter %A Eisele, Lewin %A Eklund, Niina %A Jessica Faul %A Feitosa, Mary F %A Andreas J Forstner %A Gandin, Ilaria %A Gunnarsson, Bjarni %A Halldórsson, Bjarni V %A Tamara B Harris %A Andrew C Heath %A Lynne J Hocking %A Holliday, Elizabeth G %A Homuth, Georg %A Horan, Michael A %A Jouke-Jan Hottenga %A Philip L de Jager %A Joshi, Peter K %A Jugessur, Astanand %A Marika A Kaakinen %A Kähönen, Mika %A Kanoni, Stavroula %A Keltigangas-Järvinen, Liisa %A Lambertus A Kiemeney %A Kolcic, Ivana %A Koskinen, Seppo %A Kraja, Aldi T %A Kroh, Martin %A Kutalik, Zoltán %A Latvala, Antti %A Lenore J Launer %A Lebreton, Maël P %A Douglas F Levinson %A Paul Lichtenstein %A Lichtner, Peter %A David C Liewald %A Loukola, Anu %A Pamela A F Madden %A Mägi, Reedik %A Mäki-Opas, Tomi %A Riccardo E Marioni %A Marques-Vidal, Pedro %A Meddens, Gerardus A %A McMahon, George %A Meisinger, Christa %A Meitinger, Thomas %A Milaneschi, Yusplitri %A Lili Milani %A Grant W Montgomery %A Myhre, Ronny %A Nelson, Christopher P %A Nyholt, Dale R %A William E R Ollier %A Aarno Palotie %A Paternoster, Lavinia %A Nancy L Pedersen %A Katja E Petrovic %A David J Porteous %A Katri Räikkönen %A Ring, Susan M %A Robino, Antonietta %A Rostapshova, Olga %A Rudan, Igor %A Rustichini, Aldo %A Veikko Salomaa %A Sanders, Alan R %A Sarin, Antti-Pekka %A Schmidt, Helena %A Rodney J Scott %A Smith, Blair H %A Jennifer A Smith %A Staessen, Jan A %A Steinhagen-Thiessen, Elisabeth %A Strauch, Konstantin %A Antonio Terracciano %A Tobin, Martin D %A Ulivi, Sheila %A Vaccargiu, Simona %A Quaye, Lydia %A van Rooij, Frank J A %A Venturini, Cristina %A Anna A E Vinkhuyzen %A Völker, Uwe %A Völzke, Henry %A Vonk, Judith M %A Vozzi, Diego %A Waage, Johannes %A Erin B Ware %A Gonneke Willemsen %A John R. Attia %A David A Bennett %A Klaus Berger %A Bertram, Lars %A Bisgaard, Hans %A Dorret I Boomsma %A Ingrid B Borecki %A Bültmann, Ute %A Chabris, Christopher F %A Francesco Cucca %A Cusi, Daniele %A Ian J Deary %A George Dedoussis %A Cornelia M van Duijn %A Johan G Eriksson %A Franke, Barbara %A Lude L Franke %A Paolo P. Gasparini %A Gejman, Pablo V %A Gieger, Christian %A Hans-Jörgen Grabe %A Gratten, Jacob %A Groenen, Patrick J F %A Gudnason, Vilmundur %A van der Harst, Pim %A Caroline Hayward %A Hinds, David A %A Hoffmann, Wolfgang %A Hyppönen, Elina %A Iacono, William G %A Jacobsson, Bo %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Kaprio, Jaakko %A Sharon L R Kardia %A Lehtimäki, Terho %A Lehrer, Steven F %A Patrik K E Magnusson %A Nicholas G Martin %A McGue, Matt %A Andres Metspalu %A Pendleton, Neil %A Brenda W J H Penninx %A Markus Perola %A Nicola Pirastu %A Pirastu, Mario %A Polasek, Ozren %A Posthuma, Danielle %A Power, Christine %A Province, Michael A %A Nilesh J Samani %A Schlessinger, David %A Schmidt, Reinhold %A Thorkild I. A. Sørensen %A Timothy Spector %A Stefansson, Kari %A Thorsteinsdottir, Unnur %A A. Roy Thurik %A Nicholas J Timpson %A Henning Tiemeier %A Tung, Joyce Y %A André G Uitterlinden %A Vitart, Veronique %A Vollenweider, Peter %A David R Weir %A James F Wilson %A Alan F Wright %A Dalton C Conley %A Krueger, Robert F %A George Davey Smith %A Hofman, Albert %A David I Laibson %A Sarah E Medland %A Meyer, Michelle N %A Yang, Jian %A Johannesson, Magnus %A Peter M Visscher %A Tõnu Esko %A Philipp D Koellinger %A Cesarini, David %A Daniel J. Benjamin %K Alzheimer's disease %K Bipolar Disorder %K Cognitive Ability %K Education %K Fetus %K Genome-Wide Association Study %K Humans %K Molecular Sequence Annotation %K Polymorphism, Single Nucleotide %K Schizophrenia %K United Kingdom %XEducational 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.
%B Nature %V 533 %P 539-42 %8 2016 05 26 %G eng %N 7604 %1 http://www.ncbi.nlm.nih.gov/pubmed/27225129?dopt=Abstract %R 10.1038/nature17671 %0 Journal Article %J Nature %D 2015 %T Directional dominance on stature and cognition in diverse human populations. %A Joshi, Peter K %A Tõnu Esko %A Mattsson, Hannele %A Eklund, Niina %A Gandin, Ilaria %A Nutile, Teresa %A Jackson, Anne U %A Schurmann, Claudia %A Albert Vernon Smith %A Zhang, Weihua %A Okada, Yukinori %A Stančáková, Alena %A Jessica Faul %A Wei Zhao %A Traci M Bartz %A Maria Pina Concas %A Franceschini, Nora %A Enroth, Stefan %A Vitart, Veronique %A Trompet, Stella %A Guo, Xiuqing %A Daniel I Chasman %A Jeff O'Connell %A Corre, Tanguy %A Nongmaithem, Suraj S %A Chen, Yuning %A Mangino, Massimo %A Ruggiero, Daniela %A Traglia, Michela %A Farmaki, Aliki-Eleni %A Kacprowski, Tim %A Bjonnes, Andrew %A van der Spek, Ashley %A Wu, Ying %A Giri, Anil K %A Yanek, Lisa R %A Wang, Lihua %A Edith Hofer %A Cornelius A Rietveld %A McLeod, Olga %A Marilyn C Cornelis %A Pattaro, Cristian %A Verweij, Niek %A Baumbach, Clemens %A Abdel Abdellaoui %A Warren, Helen R %A Vuckovic, Dragana %A Mei, Hao %A Bouchard, Claude %A Perry, John R B %A Cappellani, Stefania %A Saira S Mirza %A Benton, Miles C %A Broeckel, Ulrich %A Sarah E Medland %A Penelope A Lind %A Malerba, Giovanni %A Alexander W Drong %A Yengo, Loic %A Bielak, Lawrence F %A Zhi, Degui %A van der Most, Peter J %A Daniel Shriner %A Mägi, Reedik %A Hemani, Gibran %A Karaderi, Tugce %A Wang, Zhaoming %A Tian Liu %A Demuth, Ilja %A Jing Hua Zhao %A Meng, Weihua %A Lataniotis, Lazaros %A van der Laan, Sander W %A Bradfield, Jonathan P %A Andrew R Wood %A Bonnefond, Amelie %A Ahluwalia, Tarunveer S %A Hall, Leanne M %A Salvi, Erika %A Yazar, Seyhan %A Carstensen, Lisbeth %A de Haan, Hugoline G %A Abney, Mark %A Afzal, Uzma %A Matthew A. Allison %A Amin, Najaf %A Asselbergs, Folkert W %A Bakker, Stephan J L %A Barr, R Graham %A Baumeister, Sebastian E %A Daniel J. Benjamin %A Bergmann, Sven %A Boerwinkle, Eric %A Erwin P Bottinger %A Campbell, Archie %A Chakravarti, Aravinda %A Chan, Yingleong %A Chanock, Stephen J %A Chen, Constance %A Yii-Der I Chen %A Collins, Francis S %A Connell, John %A Correa, Adolfo %A Cupples, L Adrienne %A Gail Davies %A Dörr, Marcus %A Georg B Ehret %A Ellis, Stephen B %A Feenstra, Bjarke %A Feitosa, Mary F %A Ford, Ian %A Caroline S Fox %A Timothy M Frayling %A Friedrich, Nele %A Geller, Frank %A Scotland, Generation %A Gillham-Nasenya, Irina %A Gottesman, Omri %A Graff, Misa %A Grodstein, Francine %A Gu, Charles %A Haley, Chris %A Hammond, Christopher J %A Sarah E Harris %A Tamara B Harris %A Nicholas D Hastie %A Heard-Costa, Nancy L %A Heikkilä, Kauko %A Lynne J Hocking %A Homuth, Georg %A Jouke-Jan Hottenga %A Huang, Jinyan %A Huffman, Jennifer E %A Hysi, Pirro G %A Mohammed Arfan Ikram %A Ingelsson, Erik %A Joensuu, Anni %A Johansson, Åsa %A Jousilahti, Pekka %A Jukema, J Wouter %A Kähönen, Mika %A Kamatani, Yoichiro %A Kanoni, Stavroula %A Kerr, Shona M %A Khan, Nazir M %A Philipp D Koellinger %A Koistinen, Heikki A %A Kooner, Manraj K %A Kubo, Michiaki %A Kuusisto, Johanna %A Lahti, Jari %A Lenore J Launer %A Lea, Rodney A %A Lehne, Benjamin %A Lehtimäki, Terho %A David C Liewald %A Lars Lind %A Loh, Marie %A Lokki, Marja-Liisa %A London, Stephanie J %A Loomis, Stephanie J %A Loukola, Anu %A Lu, Yingchang %A Lumley, Thomas %A Lundqvist, Annamari %A Männistö, Satu %A Marques-Vidal, Pedro %A Masciullo, Corrado %A Matchan, Angela %A Mathias, Rasika A %A Matsuda, Koichi %A Meigs, James B %A Meisinger, Christa %A Meitinger, Thomas %A Menni, Cristina %A Mentch, Frank D %A Mihailov, Evelin %A Lili Milani %A Montasser, May E %A Grant W Montgomery %A Alanna C Morrison %A Myers, Richard H %A Nadukuru, Rajiv %A Navarro, Pau %A Nelis, Mari %A Nieminen, Markku S %A Ilja M Nolte %A O'Connor, George T %A Ogunniyi, Adesola %A Padmanabhan, Sandosh %A Walter R Palmas %A Pankow, James S %A Patarcic, Inga %A Pavani, Francesca %A Peyser, Patricia A %A Pietilainen, Kirsi %A Neil Poulter %A Prokopenko, Inga %A Ralhan, Sarju %A Redmond, Paul %A Rich, Stephen S %A Rissanen, Harri %A Robino, Antonietta %A Rose, Lynda M %A Rose, Richard %A Cinzia Felicita Sala %A Babatunde Salako %A Veikko Salomaa %A Sarin, Antti-Pekka %A Saxena, Richa %A Schmidt, Helena %A Scott, Laura J %A Scott, William R %A Sennblad, Bengt %A Seshadri, Sudha %A Peter Sever %A Shrestha, Smeeta %A Smith, Blair H %A Jennifer A Smith %A Soranzo, Nicole %A Sotoodehnia, Nona %A Southam, Lorraine %A Stanton, Alice V %A Stathopoulou, Maria G %A Strauch, Konstantin %A Strawbridge, Rona J %A Suderman, Matthew J %A Tandon, Nikhil %A Tang, Sian-Tsun %A Kent D Taylor %A Bamidele O Tayo %A Töglhofer, Anna Maria %A Tomaszewski, Maciej %A Tšernikova, Natalia %A Tuomilehto, Jaakko %A André G Uitterlinden %A Vaidya, Dhananjay %A van Hylckama Vlieg, Astrid %A van Setten, Jessica %A Vasankari, Tuula %A Vedantam, Sailaja %A Vlachopoulou, Efthymia %A Vozzi, Diego %A Vuoksimaa, Eero %A Waldenberger, Melanie %A Erin B Ware %A Wentworth-Shields, William %A Whitfield, John B %A Sarah Wild %A Gonneke Willemsen %A Yajnik, Chittaranjan S %A Yao, Jie %A Zaza, Gianluigi %A Zhu, Xiaofeng %A Salem, Rany M %A Melbye, Mads %A Bisgaard, Hans %A Nilesh J Samani %A Cusi, Daniele %A Mackey, David A %A Cooper, Richard S %A Froguel, Philippe %A Pasterkamp, Gerard %A Grant, Struan F A %A Hakonarson, Hakon %A Luigi Ferrucci %A Scott, Robert A %A Morris, Andrew D %A Palmer, Colin N A %A George Dedoussis %A Deloukas, Panos %A Bertram, Lars %A Lindenberger, Ulman %A Berndt, Sonja I %A Lindgren, Cecilia M %A Nicholas J Timpson %A Tönjes, Anke %A Munroe, Patricia B %A Thorkild I. A. Sørensen %A Charles N Rotimi %A Donna K Arnett %A Oldehinkel, Albertine J %A Sharon L R Kardia %A Balkau, Beverley %A Gambaro, Giovanni %A Morris, Andrew P %A Johan G Eriksson %A Margaret J Wright %A Nicholas G Martin %A Hunt, Steven C %A John M Starr %A Ian J Deary %A Griffiths, Lyn R %A Henning Tiemeier %A Nicola Pirastu %A Kaprio, Jaakko %A Wareham, Nicholas J %A Pérusse, Louis %A Wilson, James G %A Giorgia G Girotto %A Caulfield, Mark J %A Olli T Raitakari %A Dorret I Boomsma %A Gieger, Christian %A van der Harst, Pim %A Hicks, Andrew A %A Kraft, Peter %A Sinisalo, Juha %A Knekt, Paul %A Johannesson, Magnus %A Patrik K E Magnusson %A Hamsten, Anders %A Schmidt, Reinhold %A Ingrid B Borecki %A Vartiainen, Erkki %A Becker, Diane M %A Bharadwaj, Dwaipayan %A Mohlke, Karen L %A Boehnke, Michael %A Cornelia M van Duijn %A Sanghera, Dharambir K %A Teumer, Alexander %A Zeggini, Eleftheria %A Andres Metspalu %A Paolo P. Gasparini %A Ulivi, Sheila %A Ober, Carole %A Toniolo, Daniela %A Rudan, Igor %A David J Porteous %A Ciullo, Marina %A Timothy Spector %A Caroline Hayward %A Dupuis, Josée %A Ruth J F Loos %A Alan F Wright %A Chandak, Giriraj R %A Vollenweider, Peter %A Alan R Shuldiner %A Ridker, Paul M %A Rotter, Jerome I %A Sattar, Naveed %A Gyllensten, Ulf %A Kari E North %A Pirastu, Mario %A Psaty, Bruce M %A David R Weir %A Laakso, Markku %A Gudnason, Vilmundur %A Takahashi, Atsushi %A Chambers, John C %A Kooner, Jaspal S %A David P Strachan %A Campbell, Harry %A Joel N Hirschhron %A Markus Perola %A Polasek, Ozren %A James F Wilson %K Biological Evolution %K Blood pressure %K Body Height %K Cholesterol %K Cognitive Ability %K Cohort Studies %K Education %K Female %K Forced Expiratory Volume %K Genome %K Homozygote %K Humans %K Lung Volume Measurements %K Male %K Phenotype %XHomozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
%B Nature %V 523 %P 459-62 %8 2015 Jul 23 %G eng %N 7561 %1 http://www.ncbi.nlm.nih.gov/pubmed/26131930?dopt=Abstract %R 10.1038/nature14618 %0 Journal Article %J Science %D 2013 %T GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. %A Cornelius A Rietveld %A Sarah E Medland %A Derringer, Jaime %A Yang, Jian %A Tõnu Esko %A Martin, Nicolas W %A Westra, Harm-Jan %A Shakhbazov, Konstantin %A Abdel Abdellaoui %A Agrawal, Arpana %A Albrecht, Eva %A Alizadeh, Behrooz Z %A Amin, Najaf %A Barnard, John %A Baumeister, Sebastian E %A Benke, Kelly S %A Bielak, Lawrence F %A Boatman, Jeffrey A %A Patricia A. Boyle %A Gail Davies %A Christiaan de Leeuw %A Eklund, Niina %A Daniel S Evans %A Rudolf Ferhmann %A Fischer, Krista %A Gieger, Christian %A Gjessing, Håkon K %A Hägg, Sara %A Harris, Jennifer R %A Caroline Hayward %A Holzapfel, Christina %A Carla A Ibrahim-Verbaas %A Ingelsson, Erik %A Jacobsson, Bo %A Joshi, Peter K %A Jugessur, Astanand %A Marika A Kaakinen %A Kanoni, Stavroula %A Karjalainen, Juha %A Kolcic, Ivana %A Kristiansson, Kati %A Kutalik, Zoltán %A J. Lahti %A Lee, Sang H %A Lin, Peng %A Penelope A Lind %A Yongmei Liu %A Kurt Lohman %A Loitfelder, Marisa %A McMahon, George %A Vidal, Pedro Marques %A Osorio Meirelles %A Lili Milani %A Myhre, Ronny %A Nuotio, Marja-Liisa %A Christopher J Oldmeadow %A Katja E Petrovic %A Wouter J Peyrot %A Polasek, Ozren %A Quaye, Lydia %A Reinmaa, Eva %A Rice, John P %A Rizzi, Thais S %A Schmidt, Helena %A Schmidt, Reinhold %A Albert Vernon Smith %A Jennifer A Smith %A Toshiko Tanaka %A Antonio Terracciano %A van der Loos, Matthijs J H M %A Vitart, Veronique %A Völzke, Henry %A Jürgen Wellmann %A Lei Yu %A Wei Zhao %A Allik, Jüri %A John R. Attia %A Bandinelli, Stefania %A Bastardot, François %A Jonathan P. Beauchamp %A David A Bennett %A Klaus Berger %A Laura Bierut %A Dorret I Boomsma %A Bültmann, Ute %A Campbell, Harry %A Chabris, Christopher F %A Cherkas, Lynn %A Chung, Mina K %A Francesco Cucca %A de Andrade, Mariza %A Philip L de Jager %A De Neve, Jan-Emmanuel %A Ian J Deary %A George Dedoussis %A Deloukas, Panos %A Dimitriou, Maria %A Guðny Eiríksdóttir %A Elderson, Martin F %A Johan G Eriksson %A Jessica Faul %A Luigi Ferrucci %A Melissa E Garcia %A Grönberg, Henrik %A Guðnason, Vilmundur %A Hall, Per %A Harris, Juliette M %A Tamara B Harris %A Nicholas D Hastie %A Andrew C Heath %A Dena G Hernandez %A Hoffmann, Wolfgang %A Hofman, Adriaan %A Holle, Rolf %A Holliday, Elizabeth G %A Jouke-Jan Hottenga %A Iacono, William G %A Illig, Thomas %A Järvelin, Marjo-Riitta %A Kähönen, Mika %A Kaprio, Jaakko %A Kirkpatrick, Robert M %A Kowgier, Matthew %A Latvala, Antti %A Lenore J Launer %A Lawlor, Debbie A %A Lehtimäki, Terho %A Li, Jingmei %A Paul Lichtenstein %A Lichtner, Peter %A David C Liewald %A Pamela A F Madden %A Patrik K E Magnusson %A Mäkinen, Tomi E %A Masala, Marco %A McGue, Matt %A Andres Metspalu %A Mielck, Andreas %A Michael B Miller %A Grant W Montgomery %A Mukherjee, Sutapa %A Nyholt, Dale R %A Ben A Oostra %A Palmer, Lyle J %A Aarno Palotie %A Brenda W J H Penninx %A Markus Perola %A Peyser, Patricia A %A Preisig, Martin %A Katri Räikkönen %A Olli T Raitakari %A Realo, Anu %A Ring, Susan M %A Ripatti, Samuli %A Fernando Rivadeneira %A Rudan, Igor %A Rustichini, Aldo %A Veikko Salomaa %A Sarin, Antti-Pekka %A Schlessinger, David %A Rodney J Scott %A Snieder, Harold %A St Pourcain, Beate %A John M Starr %A Sul, Jae Hoon %A Surakka, Ida %A Svento, Rauli %A Teumer, Alexander %A Henning Tiemeier %A van Rooij, Frank J A %A Van Wagoner, David R %A Vartiainen, Erkki %A Viikari, Jorma %A Vollenweider, Peter %A Vonk, Judith M %A Waeber, Gérard %A David R Weir %A Wichmann, H-Erich %A Elisabeth Widen %A Gonneke Willemsen %A James F Wilson %A Alan F Wright %A Dalton C Conley %A Davey-Smith, George %A Lude L Franke %A Groenen, Patrick J F %A Hofman, Albert %A Johannesson, Magnus %A Sharon L R Kardia %A Krueger, Robert F %A David I Laibson %A Nicholas G Martin %A Meyer, Michelle N %A Posthuma, Danielle %A A. Roy Thurik %A Nicholas J Timpson %A André G Uitterlinden %A Cornelia M van Duijn %A Peter M Visscher %A Daniel J. Benjamin %A Cesarini, David %A Philipp D Koellinger %K Cognition %K Educational Status %K Endophenotypes %K Female %K Genetic Loci %K Genome-Wide Association Study %K Humans %K Male %K Multifactorial Inheritance %K Polymorphism, Single Nucleotide %XA 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) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈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.
%B Science %V 340 %P 1467-71 %8 2013 Jun 21 %G eng %N 6139 %1 http://www.ncbi.nlm.nih.gov/pubmed/23722424?dopt=Abstract %R 10.1126/science.1235488