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 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; 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

doi:10.1038/ng.3698

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 journal › Article › peer-review

177 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 language	English (US)
Pages (from-to)	1462-1472
Number of pages	11
Journal	Nature Genetics
Volume	48
Issue number	12
DOIs	https://doi.org/10.1038/ng.3698
State	Published - Oct 31 2016

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.3698

Cite this

Barban, N., Jansen, R., De Vlaming, R., Vaez, A., Mandemakers, J. J., Tropf, F. C., Shen, X., Wilson, J. F., Chasman, D. I., Nolte, I. M., Tragante, V., Van Der Laan, S. W., Perry, J. R. B., Kong, A., Ahluwalia, T. S., Albrecht, E., Yerges-Armstrong, L., Atzmon, G., Auro, K., ... Mills, M. C. (2016). Genome-wide analysis identifies 12 loci influencing human reproductive behavior. Nature Genetics, 48(12), 1462-1472. https://doi.org/10.1038/ng.3698

Barban, N, Jansen, R, De Vlaming, R, Vaez, A, Mandemakers, JJ, Tropf, FC, Shen, X, Wilson, JF, Chasman, DI, Nolte, IM, Tragante, V, Van Der Laan, SW, Perry, JRB, Kong, A, Ahluwalia, TS, Albrecht, E, Yerges-Armstrong, L, Atzmon, G, Auro, K, Ayers, K, Bakshi, A, Ben-Avraham, D, Berger, K, Bergman, A, Bertram, L, Bielak, LF, Bjornsdottir, G, Bonder, MJ, Broer, L, Bui, M, Barbieri, C, Cavadino, A, Chavarro, JE, Turman, C, Concas, MP, Cordell, HJ, Davies, G, Eibich, P, Eriksson, N, Esko, T, Eriksson, J, Falahi, F, Felix, JF, Fontana, MA, Franke, L, Gandin, I, Gaskins, AJ, Gieger, C, Gunderson, EP, Guo, X, Hayward, C, He, C, Hofer, E, Huang, H, Joshi, PK, Kanoni, S, Karlsson, R, Kiechl, S, Kifley, A, Kluttig, A, Kraft, P, Lagou, V, Lecoeur, C, Lahti, J, Li-Gao, R, Lind, PA, Liu, T, Makalic, E, Mamasoula, C, Matteson, L, Mbarek, H, McArdle, PF, McMahon, G, Meddens, SFW, Mihailov, E, Miller, M, Missmer, SA, Monnereau, C, Van Der Most, PJ, Myhre, R, Nalls, MA, Nutile, T, Kalafati, IP, Porcu, E, Prokopenko, I, Rajan, KB, Rich-Edwards, J, Rietveld, CA, Robino, A, Rose, LM, Rueedi, R, Ryan, KA, Saba, Y, Schmidt, D, Smith, JA, Stolk, L, Streeten, E, Tönjes, A, Thorleifsson, G, Ulivi, S, Wedenoja, J, Wellmann, J, Willeit, P, Yao, J, Yengo, L, Zhao, JH, Zhao, W, Zhernakova, DV, Amin, N, Andrews, H, Balkau, B, Barzilai, N, Bergmann, S, Biino, G, Bisgaard, H, Bønnelykke, K, Boomsma, DI, Buring, JE, Campbell, H, Cappellani, S, Ciullo, M, Cox, SR, Cucca, F, Toniolo, D, Davey-Smith, G, Deary, IJ, Dedoussis, G, Deloukas, P, Van Duijn, CM, De Geus, EJC, Eriksson, JG, Evans, DA, Faul, JD, Sala, CF, Froguel, P, Gasparini, P, Girotto, G, Grabe, HJ, Greiser, KH, Groenen, PJF, De Haan, HG, Haerting, J, Harris, TB, Heath, AC, Heikkilä, K, Hofman, A, Homuth, G, Holliday, EG, Hopper, J, Hyppönen, E, Jacobsson, B, Jaddoe, VWV, Johannesson, M, Jugessur, A, Kähönen, M, Kajantie, E, Kardia, SLR, Keavney, B, Kolcic, I, Koponen, P, Kovacs, P, Kronenberg, F, Kutalik, Z, La Bianca, M, Lachance, G, Iacono, WG, Lai, S, Lehtimäki, T, Liewald, DC, Lindgren, CM, Liu, Y, Luben, R, Lucht, M, Luoto, R, Magnus, P, Magnusson, P, Martin, NG, McGue, M, McQuillan, R, Medland, SE, Meisinger, C, Mellström, D, Metspalu, A, Traglia, M, Milani, L, Mitchell, P, Montgomery, GW, Mook-Kanamori, D, De Mutsert, R, Nohr, EA, Ohlsson, C, Olsen, J, Ong, KK, Paternoster, L, Pattie, A, Penninx, BWJH, Perola, M, Peyser, PA, Pirastu, M, Polasek, O, Power, C, Kaprio, J, Raffel, LJ, Räikkönen, K, Raitakari, O, Ridker, PM, Ring, SM, Roll, K, Rudan, I, Ruggiero, D, Rujescu, D, Salomaa, V, Schlessinger, D, Schmidt, H, Schmidt, R, Schupf, N, Smit, J, Sorice, R, Spector, TD, Starr, JM, Stöckl, D, Strauch, K, Stumvoll, M, Swertz, MA, Thorsteinsdottir, U, Roy Thurik, A, Timpson, NJ, Tung, JY, Uitterlinden, AG, Vaccargiu, S, Viikari, J, Vitart, V, Völzke, H, Vollenweider, P, Vuckovic, D, Waage, J, Wagner, GG, Wang, JJ, Wareham, NJ, Weir, DR, Willemsen, G, Willeit, J, Wright, AF, Zondervan, KT, Stefansson, K, Krueger, RF, Lee, JJ, Benjamin, DJ, Cesarini, D, Koellinger, PD, Den Hoed, M, Snieder, H & Mills, MC 2016, 'Genome-wide analysis identifies 12 loci influencing human reproductive behavior', Nature Genetics, vol. 48, no. 12, pp. 1462-1472. https://doi.org/10.1038/ng.3698

@article{f22edd643e1342408905d7a09ea64456,

title = "Genome-wide analysis identifies 12 loci influencing human reproductive behavior",

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.",

author = "Nicola Barban and Rick Jansen and {De Vlaming}, Ronald and Ahmad Vaez and Mandemakers, {Jornt J.} and Tropf, {Felix C.} and Xia Shen and Wilson, {James F.} and Chasman, {Daniel I.} and Nolte, {Ilja M.} and Vinicius Tragante and {Van Der Laan}, {Sander W.} and Perry, {John R.B.} and Augustine Kong and Ahluwalia, {Tarunveer S.} and Eva Albrecht and Laura Yerges-Armstrong and Gil Atzmon and Kirsi Auro and Kristin Ayers and Andrew Bakshi and Danny Ben-Avraham and Klaus Berger and Aviv Bergman and Lars Bertram and Bielak, {Lawrence F.} and Gyda Bjornsdottir and Bonder, {Marc Jan} and Linda Broer and Minh Bui and Caterina Barbieri and Alana Cavadino and Chavarro, {Jorge E.} and Constance Turman and Concas, {Maria Pina} and Cordell, {Heather J.} and Gail Davies and Peter Eibich and Nicholas Eriksson and T{\~o}nu Esko and Joel Eriksson and Fahimeh Falahi and Felix, {Janine F.} and Fontana, {Mark Alan} and Lude Franke and Ilaria Gandin and Gaskins, {Audrey J.} and Christian Gieger and Gunderson, {Erica P.} and Xiuqing Guo and Caroline Hayward and Chunyan He and Edith Hofer and Hongyan Huang and Joshi, {Peter K.} and Stavroula Kanoni and Robert Karlsson and Stefan Kiechl and Annette Kifley and Alexander Kluttig and Peter Kraft and Vasiliki Lagou and Cecile Lecoeur and Jari Lahti and Ruifang Li-Gao and Lind, {Penelope A.} and Tian Liu and Enes Makalic and Crysovalanto Mamasoula and Lindsay Matteson and Hamdi Mbarek and McArdle, {Patrick F.} and George McMahon and Meddens, {S. Fleur W.} and Evelin Mihailov and Mike Miller and Missmer, {Stacey A.} and Claire Monnereau and {Van Der Most}, {Peter J.} and Ronny Myhre and Nalls, {Mike A.} and Teresa Nutile and Kalafati, {Ioanna Panagiota} and Eleonora Porcu and Inga Prokopenko and Rajan, {Kumar B.} and Janet Rich-Edwards and Rietveld, {Cornelius A.} and Antonietta Robino and Rose, {Lynda M.} and Rico Rueedi and Ryan, {Kathleen A.} and Yasaman Saba and Daniel Schmidt and Smith, {Jennifer A.} and Lisette Stolk and Elizabeth Streeten and Anke T{\"o}njes and Gudmar Thorleifsson and Sheila Ulivi and Juho Wedenoja and Juergen Wellmann and Peter Willeit and Jie Yao and Loic Yengo and Zhao, {Jing Hua} and Wei Zhao and Zhernakova, {Daria V.} and Najaf Amin and Howard Andrews and Beverley Balkau and Nir Barzilai and Sven Bergmann and Ginevra Biino and Hans Bisgaard and Klaus B{\o}nnelykke and Boomsma, {Dorret I.} and Buring, {Julie E.} and Harry Campbell and Stefania Cappellani and Marina Ciullo and Cox, {Simon R.} and Francesco Cucca and Daniela Toniolo and George Davey-Smith and Deary, {Ian J.} and George Dedoussis and Panos Deloukas and {Van Duijn}, {Cornelia M.} and {De Geus}, {Eco J.C.} and Eriksson, {Johan G.} and Evans, {Denis A.} and Faul, {Jessica D.} and Sala, {Cinzia Felicita} and Philippe Froguel and Paolo Gasparini and Giorgia Girotto and Grabe, {Hans J{\"o}rgen} and Greiser, {Karin Halina} and Groenen, {Patrick J.F.} and {De Haan}, {Hugoline G.} and Johannes Haerting and Harris, {Tamara B.} and Heath, {Andrew C.} and Kauko Heikkil{\"a} and Albert Hofman and Georg Homuth and Holliday, {Elizabeth G.} and John Hopper and Elina Hypp{\"o}nen and Bo Jacobsson and Jaddoe, {Vincent W.V.} and Magnus Johannesson and Astanand Jugessur and Mika K{\"a}h{\"o}nen and Eero Kajantie and Kardia, {Sharon L.R.} and Bernard Keavney and Ivana Kolcic and P{\"a}ivikki Koponen and Peter Kovacs and Florian Kronenberg and Zoltan Kutalik and {La Bianca}, Martina and Genevieve Lachance and Iacono, {William G.} and Sandra Lai and Terho Lehtim{\"a}ki and Liewald, {David C.} and Lindgren, {Cecilia M.} and Yongmei Liu and Robert Luben and Michael Lucht and Riitta Luoto and Per Magnus and Patrikke Magnusson and Martin, {Nicholas G.} and Matt McGue and Ruth McQuillan and Medland, {Sarah E.} and Christa Meisinger and Dan Mellstr{\"o}m and Andres Metspalu and Michela Traglia and Lili Milani and Paul Mitchell and Montgomery, {Grant W.} and Dennis Mook-Kanamori and {De Mutsert}, Ren{\'e}e and Nohr, {Ellen A.} and Claes Ohlsson and J{\o}rn Olsen and Ong, {Ken K.} and Lavinia Paternoster and Alison Pattie and Penninx, {Brenda W.J.H.} and Markus Perola and Peyser, {Patricia A.} and Mario Pirastu and Ozren Polasek and Chris Power and Jaakko Kaprio and Raffel, {Leslie J.} and Katri R{\"a}ikk{\"o}nen and Olli Raitakari and Ridker, {Paul M.} and Ring, {Susan M.} and Kathryn Roll and Igor Rudan and Daniela Ruggiero and Dan Rujescu and Veikko Salomaa and David Schlessinger and Helena Schmidt and Reinhold Schmidt and Nicole Schupf and Johannes Smit and Rossella Sorice and Spector, {Tim D.} and Starr, {John M.} and Doris St{\"o}ckl and Konstantin Strauch and Michael Stumvoll and Swertz, {Morris A.} and Unnur Thorsteinsdottir and {Roy Thurik}, A. and Timpson, {Nicholas J.} and Tung, {Joyce Y.} and Uitterlinden, {Andr{\'e} G.} and Simona Vaccargiu and Jorma Viikari and Veronique Vitart and Henry V{\"o}lzke and Peter Vollenweider and Dragana Vuckovic and Johannes Waage and Wagner, {Gert G.} and Wang, {Jie Jin} and Wareham, {Nicholas J.} and Weir, {David R.} and Gonneke Willemsen and Johann Willeit and Wright, {Alan F.} and Zondervan, {Krina T.} and Kari Stefansson and Krueger, {Robert F.} and Lee, {James J.} and Benjamin, {Daniel J.} and David Cesarini and Koellinger, {Philipp D.} and {Den Hoed}, Marcel and Harold Snieder and Mills, {Melinda C.}",

year = "2016",

month = oct,

day = "31",

doi = "10.1038/ng.3698",

language = "English (US)",

volume = "48",

pages = "1462--1472",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "12",

}

TY - JOUR

T1 - Genome-wide analysis identifies 12 loci influencing human reproductive behavior

AU - Barban, Nicola

AU - Jansen, Rick

AU - De Vlaming, Ronald

AU - Vaez, Ahmad

AU - Mandemakers, Jornt J.

AU - Tropf, Felix C.

AU - Shen, Xia

AU - Wilson, James F.

AU - Chasman, Daniel I.

AU - Nolte, Ilja M.

AU - Tragante, Vinicius

AU - Van Der Laan, Sander W.

AU - Perry, John R.B.

AU - Kong, Augustine

AU - Ahluwalia, Tarunveer S.

AU - Albrecht, Eva

AU - Yerges-Armstrong, Laura

AU - Atzmon, Gil

AU - Auro, Kirsi

AU - Ayers, Kristin

AU - Bakshi, Andrew

AU - Ben-Avraham, Danny

AU - Berger, Klaus

AU - Bergman, Aviv

AU - Bertram, Lars

AU - Bielak, Lawrence F.

AU - Bjornsdottir, Gyda

AU - Bonder, Marc Jan

AU - Broer, Linda

AU - Bui, Minh

AU - Barbieri, Caterina

AU - Cavadino, Alana

AU - Chavarro, Jorge E.

AU - Turman, Constance

AU - Concas, Maria Pina

AU - Cordell, Heather J.

AU - Davies, Gail

AU - Eibich, Peter

AU - Eriksson, Nicholas

AU - Esko, Tõnu

AU - Eriksson, Joel

AU - Falahi, Fahimeh

AU - Felix, Janine F.

AU - Fontana, Mark Alan

AU - Franke, Lude

AU - Gandin, Ilaria

AU - Gaskins, Audrey J.

AU - Gieger, Christian

AU - Gunderson, Erica P.

AU - Guo, Xiuqing

AU - Hayward, Caroline

AU - He, Chunyan

AU - Hofer, Edith

AU - Huang, Hongyan

AU - Joshi, Peter K.

AU - Kanoni, Stavroula

AU - Karlsson, Robert

AU - Kiechl, Stefan

AU - Kifley, Annette

AU - Kluttig, Alexander

AU - Kraft, Peter

AU - Lagou, Vasiliki

AU - Lecoeur, Cecile

AU - Lahti, Jari

AU - Li-Gao, Ruifang

AU - Lind, Penelope A.

AU - Liu, Tian

AU - Makalic, Enes

AU - Mamasoula, Crysovalanto

AU - Matteson, Lindsay

AU - Mbarek, Hamdi

AU - McArdle, Patrick F.

AU - McMahon, George

AU - Meddens, S. Fleur W.

AU - Mihailov, Evelin

AU - Miller, Mike

AU - Missmer, Stacey A.

AU - Monnereau, Claire

AU - Van Der Most, Peter J.

AU - Myhre, Ronny

AU - Nalls, Mike A.

AU - Nutile, Teresa

AU - Kalafati, Ioanna Panagiota

AU - Porcu, Eleonora

AU - Prokopenko, Inga

AU - Rajan, Kumar B.

AU - Rich-Edwards, Janet

AU - Rietveld, Cornelius A.

AU - Robino, Antonietta

AU - Rose, Lynda M.

AU - Rueedi, Rico

AU - Ryan, Kathleen A.

AU - Saba, Yasaman

AU - Schmidt, Daniel

AU - Smith, Jennifer A.

AU - Stolk, Lisette

AU - Streeten, Elizabeth

AU - Tönjes, Anke

AU - Thorleifsson, Gudmar

AU - Ulivi, Sheila

AU - Wedenoja, Juho

AU - Wellmann, Juergen

AU - Willeit, Peter

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PY - 2016/10/31

Y1 - 2016/10/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84992744163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992744163&partnerID=8YFLogxK

U2 - 10.1038/ng.3698

DO - 10.1038/ng.3698

M3 - Article

C2 - 27798627

AN - SCOPUS:84992744163

SN - 1061-4036

VL - 48

SP - 1462

EP - 1472

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Genome-wide analysis identifies 12 loci influencing human reproductive behavior

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