Year: 2016
Type: article
Study design: Observational Study
Abstract: Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior. The 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.
Source: Nature Genetics
DOI: 10.1038/ng.3698
Authors: Nicola Barban, LifeLines Cohort Study, Rick Jansen, Ronald de Vlaming, Ahmad Vaez, Jornt J Mandemakers, Felix C Tropf, Xia Shen, James F Wilson, Daniel I Chasman, Ilja M Nolte, Vinicius Tragante, Sander W van der Laan, John R B Perry, Augustine Kong, Tarunveer S Ahluwalia, Eva Albrecht, Laura Yerges-Armstrong, Gil Atzmon, Kirsi Auro, Kristin Ayers, Andrew Bakshi, Danny Ben-Avraham, Klaus Berger, Aviv Bergman, Lars Bertram, Lawrence F Bielak, Gyda Bjornsdottir, Marc Jan Bonder, Linda Broer, Minh Bui, Caterina Barbieri, Alana Cavadino, Jorge E Chavarro, Constance Turman, Maria Pina Concas, Heather J Cordell, Gail Davies, Peter Eibich, Nicholas Eriksson, Tõnu Esko, Joel Eriksson, Fahimeh Falahi, Janine F Felix, Mark Alan Fontana, Lude Franke, Ilaria Gandin, Audrey J Gaskins, Christian Gieger, Erica P Gunderson, Xiuqing Guo, Caroline Hayward, Chunyan He, Edith Hofer, Hongyan Huang, Peter K Joshi, Stavroula Kanoni, Robert Karlsson, Stefan Kiechl, Annette Kifley, Alexander Kluttig, Peter Kraft, Vasiliki Lagou, Cecile Lecoeur, Jari Lahti, Ruifang Li-Gao, Penelope A Lind, Tian Liu, Enes Makalic, Crysovalanto Mamasoula, Lindsay Matteson, Hamdi Mbarek, Patrick F McArdle, George McMahon, S Fleur W Meddens, Evelin Mihailov, Mike Miller, Stacey A Missmer, Claire Monnereau, Peter J van der Most, Ronny Myhre, Mike A Nalls, Teresa Nutile, Ioanna Panagiota Kalafati, Eleonora Porcu, Inga Prokopenko, Kumar B Rajan, Janet Rich-Edwards, Cornelius A Rietveld, Antonietta Robino, Lynda M Rose, Rico Rueedi, Kathleen A Ryan, Yasaman Saba, Daniel Schmidt, Jennifer A Smith, Lisette Stolk, Elizabeth Streeten, Anke Tönjes, Gudmar Thorleifsson, Sheila Ulivi, Juho Wedenoja, Juergen Wellmann, Peter Willeit, Jie Yao, Loic Yengo, Jing Hua Zhao, Wei Zhao, Daria V Zhernakova, Najaf Amin, Howard Andrews, Beverley Balkau, Nir Barzilai, Sven Bergmann, Ginevra Biino, Hans Bisgaard, Klaus Bønnelykke, Dorret I Boomsma, Julie E Buring, Harry Campbell, Stefania Cappellani, Marina Ciullo, Simon R Cox, Francesco Cucca, Daniela Toniolo, George Davey-Smith, Ian J Deary, George Dedoussis, Panos Deloukas, Cornelia M van Duijn, Eco J C de Geus, Johan G Eriksson, Denis A Evans, Jessica D Faul, Cinzia Felicita Sala, Philippe Froguel, Paolo Gasparini, Giorgia Girotto, Hans-Jörgen Grabe, Karin Halina Greiser, Patrick J F Groenen, Hugoline G de Haan, Johannes Haerting, Tamara B Harris, Andrew C Heath, Kauko Heikkilä, Albert Hofman, Georg Homuth, Elizabeth G Holliday, John Hopper, Elina Hyppönen, Bo Jacobsson, Vincent W V Jaddoe, Magnus Johannesson, Astanand Jugessur, Mika Kähönen, Eero Kajantie, Sharon L R Kardia, Bernard Keavney, Ivana Kolcic, Päivikki Koponen, Peter Kovacs, Florian Kronenberg, Zoltan Kutalik, Martina La Bianca, Genevieve Lachance, William G Iacono, Sandra Lai, Terho Lehtimäki, David C Liewald, Cecilia M Lindgren, Yongmei Liu, Robert Luben, Michael Lucht, Riitta Luoto, Per Magnus, Patrik K E Magnusson, Nicholas G Martin, Matt McGue, Ruth McQuillan, Sarah E Medland, Christa Meisinger, Dan Mellström, Andres Metspalu, Michela Traglia, Lili Milani, Paul Mitchell, Grant W Montgomery, Dennis Mook-Kanamori, Renée de Mutsert, Ellen A Nohr, Claes Ohlsson, Jørn Olsen, Ken K Ong, Lavinia Paternoster, Alison Pattie, Brenda W J H Penninx, Markus Perola, Patricia A Peyser, Mario Pirastu, Ozren Polasek, Chris Power, Jaakko Kaprio, Leslie J Raffel, Katri Räikkönen, Olli Raitakari, Paul M Ridker, Susan M Ring, Kathryn Roll, Igor Rudan, Daniela Ruggiero, Dan Rujescu, Veikko Salomaa, David Schlessinger, Helena Schmidt, Reinhold Schmidt, Nicole Schupf, Johannes Smit, Rossella Sorice, Tim D Spector, John M Starr, Doris Stöckl, Konstantin Strauch, Michael Stumvoll, Morris A Swertz, Unnur Thorsteinsdottir, A Roy Thurik, Nicholas J Timpson, Joyce Y Tung, André G Uitterlinden, Simona Vaccargiu, Jorma Viikari, Veronique Vitart, Henry Völzke, Peter Vollenweider, Dragana Vuckovic, Johannes Waage, Gert G Wagner, Jie Jin Wang, Nicholas J Wareham, David R Weir, Gonneke Willemsen, Johann Willeit, Alan F Wright, Krina T Zondervan, Kari Stefansson, Robert F Krueger, James J Lee, Daniel J Benjamin, David Cesarini, Philipp D Koellinger, Marcel den Hoed, Harold Snieder, Melinda C Mills
Institutions: University of Oxford, Lifelines, Amsterdam UMC Location Vrije Universiteit Amsterdam, Erasmus MC, Erasmus University Rotterdam, Isfahan University of Medical Sciences, University Medical Center Groningen, University of Groningen, Wageningen University & Research, Karolinska Institutet, Institute of Genetics and Cancer, MRC Human Genetics Unit, University of Edinburgh, Brigham and Women's Hospital, Harvard University, University Medical Center Utrecht, University of Cambridge, Wellcome/MRC Institute of Metabolic Science, MRC Epidemiology Unit, deCODE Genetics (Iceland), University of Iceland, University of Copenhagen, Novo Nordisk Foundation, Gentofte Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Novo Nordisk Foundation Center for Basic Metabolic Research, Helmholtz Munich, University of Maryland, Baltimore, Albert Einstein College of Medicine, University of Helsinki, Finnish Institute for Health and Welfare, Institute for Molecular Medicine Finland, University of Haifa, Newcastle University, The University of Queensland, University of Münster, Institute for Integrative and Experimental Genomics, Imperial College London, University of Lübeck, University of Michigan, The University of Melbourne, IRCCS Ospedale San Raffaele, Queen Mary University of London, University College London, Institute of Genetic and Biomedical Research, National Research Council, 23andMe (United States), Broad Institute, University of Tartu, University of Gothenburg, Helsinki University Hospital, Vaasa Central Hospital, Folkhälsans Forskningscentrum, University of Southern California, University of Trieste, Kaiser Permanente, Kaiser Permanente Northern California, University of California, Los Angeles, The Lundquist Institute, Harbor–UCLA Medical Center, Indiana University, Medical University of Graz, William Harvey Research Institute, Innsbruck Medical University, Universität Innsbruck, The University of Sydney, Westmead Institute for Medical Research, Martin Luther University Halle-Wittenberg, KU Leuven, Centre National de la Recherche Scientifique, Université de Lille, Institut Pasteur de Lille, Leiden University Medical Center, QIMR Berghofer Medical Research Institute, Max Planck Institute for Human Development, Max Planck Institute for Molecular Genetics, University of Minnesota, University of Minnesota System, Amsterdam Public Health, Vrije Universiteit Amsterdam, University of Bristol, Norwegian Institute of Public Health, National Institutes of Health, National Institute on Aging, Institute of Genetics and Biophysics, Harokopio University of Athens, University of Sassari, Rush University Medical Center, Centre for Human Genetics, Oxford Centre for Diabetes, Endocrinology and Metabolism, IRCCS Materno Infantile Burlo Garofolo, University of Lausanne, SIB Swiss Institute of Bioinformatics, Leipzig University, King's College London, New York State Psychiatric Institute, Istituto di Genetica Molecolare, Istituto Neurologico Mediterraneo, MRC Integrative Epidemiology Unit, King Abdulaziz University, Institute for Social Research, Universitätsmedizin Greifswald, German Cancer Research Center, Hunter Medical Research Institute, University of Newcastle Australia, University of South Australia, South Australian Health and Medical Research Institute, Stockholm School of Economics, Tampere University Hospital, University of Tampere, Oulu University Hospital, Helsinki Children's Hospital, University of Oulu, University of Manchester, University of Split, IFB Adiposity Diseases, Centre Hospitalier Universitaire Vaudois, Institute of Social and Preventive Medicine, Fimlab (Finland), NIHR Oxford Biomedical Research Centre, Wake Forest University Health Sciences, Wake Forest University, Urho Kaleva Kekkonen Institute, University of Southern Denmark, King Faisal Specialist Hospital & Research Centre, Aarhus University, Cedars-Sinai Medical Center, University of Turku, Turku University Hospital, Columbia University Irving Medical Center, Alzheimer Scotland, Ludwig-Maximilians-Universität München, MBS School of Business, Technische Universität Berlin, National Bureau of Economic Research, New York University, Research Institute of Industrial Economics, Uppsala University, Science for Life Laboratory
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: National Science Foundation, U.S. Department of Veterans Affairs, University of Southern California, Wellcome Trust, International Seafood Sustainability Foundation, National Institute for Health and Care Research, British Heart Foundation, University of Oxford, European Commission, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Lundbeckfonden, Hjärt-Lungfonden, Vetenskapsrådet, Novo Nordisk Fonden, National Institutes of Health, Medical Research Council, Economic and Social Research Council, ESRC National Centre for Research Methods, University of Southampton, National Institute on Aging, National Center for Advancing Translational Sciences, H2020 European Research Council
Awards: G1365915403, G1493513681, G1768685568, NIHR Senior Investigator Award, G2620930830, G2638643893, Investigation of genetic mechanisms underlying susceptibility to complex congenital and arrhythmic cardiovascular disease. (Renewal), G3165234770, UCLA Clinical and Translational Science Institute, National Alzheimer's Coordinating Center, G3343291977, SOCGEN: Combining Social Science and Molecular Genetic Research to Examine Inequality and the Life Course, G3445821079, G3467173285, G3682927731, G385201875, Nonlinear Models of Cognition Preceding AD in a Biracial Population Sample, G4556158994, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., G4696716500, G5062693174, G5067462658, NBER Training Program in Aging and Health Economics, G5517677352, G5594923810, Identifying targets and compounds for the therapeutic intervention of coronary heart disease using a zebrafish model system, The molecular genetic architecture of educational attainment and its significance for cognitive health, G6064539666, Changing families and sustainable societies: Policy contexts and diversity over the life course and across generations, Einstein's Nathan Shock Center of Excellence in Basic Biology of Aging, G6957823285, G7423759087, NIHR Senior Investigator Award, G8137569311, Genome-Wide Analyses of Health and Well-Being Phenotypes, G8757811150, Understanding and Improving Healthcare Decision-Making and Outcomes for People Living with Alzheimer's Disease and Related Dementias, NBER Center for Aging and Health Research, UCLA Clinical and Translational Science Institute
OpenAlex ID: W2544485223