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Genome-wide analysis identifies 12 loci influencing human reproductive behavior

Lookup NU author(s): Dr Kristin Ayers, Professor Heather Cordell, Valentina Mamasoula, Professor Bernard Keavney

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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.


Publication metadata

Author(s): 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 XQ, Hayward C, He CY, Hofer E, Huang HY, Joshi PK, Kanoni S, Karlsson R, Kiechl S, Kifley A, Kluttig A, Kraft P, Lagou V, Lecoeur C, Lahti J, Li-Gao RF, 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, Tonjes 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, Bonnelykke 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, Heikkila K, Hofman A, Homuth G, Holliday EG, Hopper J, Hypponen E, Jacobsson B, Jaddoe' VWV, Johannesson M, Kahonen 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, Lehtimaki T, Liewald DC, Lindgren CM, Liu YM, Luben R, Lucht M, Luoto R, Magnus P, Magnusson PKE, Martin NG, McGue M, McQuillan R, Medland SE, Meisinger C, Mellstrom D, Metspalu A, Traglia M, Milani L, Mitchell P, Montgomery GW, Mook-Kanamori D, de Mutsert R, Nohr EA, Ohlsson C, Olsen P, Ong KK, Paternoster L, Pattie A, Penninx BWJH, Perola M, Peyser PA, Pirastu M, Polasek O, Power C, Kaprio J, Raffel LJ, Raikkonen 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, Stockl D, Strauch K, Stumvoll M, Swertz MA, Thorsteinsdottir U, Thurik AR, Timpson NJ, Tung JY, Uitterlinden AG, Vaccargiu S, Viikari J, Vitart V, Volzke 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, Bios Consortium, LifeLines Cohort Study

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2016

Volume: 48

Issue: 12

Pages: 1462-1472

Print publication date: 01/12/2016

Online publication date: 31/10/2016

Acceptance date: 22/09/2016

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng.3698

DOI: 10.1038/ng.3698


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Funding

Funder referenceFunder name
Pershing Square Fund of the Foundations of Human Behavior
Jan Wallander and Tom Hedelius Foundation
John Fell Fund
National Institutes of Health Office of Behavioral and Social Science Research
US National Science Foundation (EAGER: 'Workshop for the Formation of a Social Science Genetic Association Consortium')
Wellcome Trust ISSF
20140543Swedish Heart-Lung Foundation
2015-03657Swedish Research Council
320116European Union
421-2013-1061Swedish Research Council
452-10-012Dutch Science Foundation (NWO) grant (VIDI grant)
537-2014-371Swedish Research Council
615603ERC Consolidator Grant SOCIOGENOME
647648 EdGeERC
E9/11Ragnar Soderberg Foundation
ES/N011856/1UK ESRC/NCRM SOCGEN grant
P01-AG005842NIA/NIH
P01-AG005842-20S2NIA/NIH
P30-AG012810NIA/NIH
R01-AG042568-02NIA/NIH
T32-AG000186-23NIA/NIH

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