Genome-wide analysis identifies 12 loci influencing human reproductive behavior

N Barban, R Jansen, Ronald Vlaming, A Vaez, JJ Mandemakers, FC Tropf, X Shen, JF Wilson, DI Chasman, IM (Ilja) Nolte, V Tragante, SW van der Laan, JRB Perry, A Kong, TS Ahluwalia, E Albrecht, L Yerges-Armstrong, G Atzmon, K Auro, K AyersA Bakshi, D Ben-Avraham, K Berger, A Bergman, L Bertram, LF Bielak, G Bjornsdottir, MJ Bonder, Linda Broer, M Bui, C Barbieri, A Cavadino, JE Chavarro, C Turman, MP Concas, HJ Cordell, G Davies, P Eibich, N Eriksson, T Esko, J Eriksson, F Falahi, Janine Felix, MA Fontana, L Franke, I Gandin, AJ Gaskins, C Gieger, EP Gunderson, XQ Guo, C Hayward, CY He, E Hofer, HY Huang, PK Joshi, S Kanoni, R Karlsson, S Kiechl, A Kifley, A Kluttig, P Kraft, V Lagou, C Lecoeur, J Lahti, RF Li-Gao, PA Lind, T Liu, E Makalic, C Mamasoula, L Matteson, H Mbarek, PF McArdle, G McMahon, SFW Meddens, E Mihailov, M Miller, SA Missmer, Claire Monnereau, PJ van der Most, R Myhre, MA Nalls, T Nutile, IP Kalafati, E Porcu, I Prokopenko, KB Rajan, J Rich-Edwards, Niels Rietveld, A Robino, LM Rose, R Rueedi, KA Ryan, Y Saba, D Schmidt, JA Smith, Lisette Stolk, E Streeten, A Tonjes, G Thorleifsson, S Ulivi, J Wedenoja, J Wellmann, P Willeit, J Yao, L Yengo, JH Zhao, W Zhao, DV Zhernakova, Najaf Amin, H Andrews, B Balkau, N Barzilai, S Bergmann, G Biino, H Bisgaard, K Bonnelykke, DI Boomsma, JE Buring, H Campbell, S Cappellani, M Ciullo, SR Cox, F Cucca, D Toniolo, G Davey-Smith, IJ Deary, G Dedoussis, P Deloukas, Cornelia Duijn, EJC de Geus, JG Eriksson, DA Evans, JD Faul, CF Sala, P Froguel, P Gasparini, G Girotto, HJ Grabe, KH Greiser, Patrick Groenen, HG de Haan, J Haerting, TB Harris, AC Heath, K Heikkila, Bert Hofman, G Homuth, EG Holliday, J Hopper, E Hypponen, B Jacobsson, Vincent Jaddoe, M Johannesson, M Kahonen, E Kajantie, SLR Kardia, B Keavney, I Kolcic, P Koponen, P Kovacs, F Kronenberg, Z Kutalik, M La Bianca, G Lachance, WG Iacono, S Lai, T Lehtimaki, DC Liewald, CM Lindgren, YM Liu, R Luben, M Lucht, R Luoto, P Magnus, PKE Magnusson, NG Martin, M McGue, R McQuillan, SE Medland, C Meisinger, D Mellstrom, A Metspalu, M Traglia, L Milani, P Mitchell, GW Montgomery, D Mook-Kanamori, R de Mutsert, EA Nohr, C Ohlsson, P Olsen, KK Ong, L Paternoster, A Pattie, BWJH Penninx, M Perola, PA Peyser, M Pirastu, O Polasek, C Power, J Kaprio, LJ Raffel, K Raikkonen, O Raitakari, PM Ridker, SM Ring, K Roll, I Rudan, D Ruggiero, D Rujescu, V Salomaa, D Schlessinger, Heléna Schmidt, R Schmidt, N Schupf, J Smit, R Sorice, TD Spector, JM Starr, D Stockl, K Strauch, M Stumvoll, MA Swertz, U Thorsteinsdottir, AR Thurik, NJ Timpson, JY Tung, André Uitterlinden, S Vaccargiu, J Viikari, V Vitart, H Volzke, P Vollenweider, D Vuckovic, J Waage, GG Wagner, JJ Wang, NJ Wareham, DR Weir, G Willemsen, J Willeit, AF Wright, KT Zondervan, K Stefansson, RF Krueger, JJ Lee, DJ Benjamin, D Cesarini, PD Koellinger, M den Hoed, H Snieder, MC Mills, Roy Thurik

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184 Citations (Scopus)

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
Publication statusPublished - 2016

Research programs

  • EUR ESE 31
  • EMC MM-01-39-09-A
  • EMC MM-04-54-08-A
  • EMC NIHES-01-64-02

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