Genome-wide analysis identifies 12 loci influencing human reproductive behavior

Nicola Barban, 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 AyersAndrew 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, Patrikke 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

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1462-1472
Number of pages11
JournalNature Genetics
Volume48
Issue number12
DOIs
StatePublished - Oct 31 2016

Funding

FundersFunder number
National Institute on AgingZIAAG000647
National Institute on Aging

    ASJC Scopus subject areas

    • Genetics

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