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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.

SUBMITTER: Barban N 

PROVIDER: S-EPMC5695684 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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

Barban Nicola N   Jansen Rick R   de Vlaming Ronald R   Vaez Ahmad A   Mandemakers Jornt J JJ   Tropf Felix C FC   Shen Xia X   Wilson James F JF   Chasman Daniel I DI   Nolte Ilja M IM   Tragante Vinicius V   van der Laan Sander W SW   Perry John R B JR   Kong Augustine A   Ahluwalia Tarunveer S TS   Albrecht Eva E   Yerges-Armstrong Laura L   Atzmon Gil G   Auro Kirsi K   Ayers Kristin K   Bakshi Andrew A   Ben-Avraham Danny D   Berger Klaus K   Bergman Aviv A   Bertram Lars L   Bielak Lawrence F LF   Bjornsdottir Gyda G   Bonder Marc Jan MJ   Broer Linda L   Bui Minh M   Barbieri Caterina C   Cavadino Alana A   Chavarro Jorge E JE   Turman Constance C   Concas Maria Pina MP   Cordell Heather J HJ   Davies Gail G   Eibich Peter P   Eriksson Nicholas N   Esko Tõnu T   Eriksson Joel J   Falahi Fahimeh F   Felix Janine F JF   Fontana Mark Alan MA   Franke Lude L   Gandin Ilaria I   Gaskins Audrey J AJ   Gieger Christian C   Gunderson Erica P EP   Guo Xiuqing X   Hayward Caroline C   He Chunyan C   Hofer Edith E   Huang Hongyan H   Joshi Peter K PK   Kanoni Stavroula S   Karlsson Robert R   Kiechl Stefan S   Kifley Annette A   Kluttig Alexander A   Kraft Peter P   Lagou Vasiliki V   Lecoeur Cecile C   Lahti Jari J   Li-Gao Ruifang R   Lind Penelope A PA   Liu Tian T   Makalic Enes E   Mamasoula Crysovalanto C   Matteson Lindsay L   Mbarek Hamdi H   McArdle Patrick F PF   McMahon George G   Meddens S Fleur W SF   Mihailov Evelin E   Miller Mike M   Missmer Stacey A SA   Monnereau Claire C   van der Most Peter J PJ   Myhre Ronny R   Nalls Mike A MA   Nutile Teresa T   Kalafati Ioanna Panagiota IP   Porcu Eleonora E   Prokopenko Inga I   Rajan Kumar B KB   Rich-Edwards Janet J   Rietveld Cornelius A CA   Robino Antonietta A   Rose Lynda M LM   Rueedi Rico R   Ryan Kathleen A KA   Saba Yasaman Y   Schmidt Daniel D   Smith Jennifer A JA   Stolk Lisette L   Streeten Elizabeth E   Tönjes Anke A   Thorleifsson Gudmar G   Ulivi Sheila S   Wedenoja Juho J   Wellmann Juergen J   Willeit Peter P   Yao Jie J   Yengo Loic L   Zhao Jing Hua JH   Zhao Wei W   Zhernakova Daria V DV   Amin Najaf N   Andrews Howard H   Balkau Beverley B   Barzilai Nir N   Bergmann Sven S   Biino Ginevra G   Bisgaard Hans H   Bønnelykke Klaus K   Boomsma Dorret I DI   Buring Julie E JE   Campbell Harry H   Cappellani Stefania S   Ciullo Marina M   Cox Simon R SR   Cucca Francesco F   Toniolo Daniela D   Davey-Smith George G   Deary Ian J IJ   Dedoussis George G   Deloukas Panos P   van Duijn Cornelia M CM   de Geus Eco J C EJ   Eriksson Johan G JG   Evans Denis A DA   Faul Jessica D JD   Sala Cinzia Felicita CF   Froguel Philippe P   Gasparini Paolo P   Girotto Giorgia G   Grabe Hans-Jörgen HJ   Greiser Karin Halina KH   Groenen Patrick J F PJ   de Haan Hugoline G HG   Haerting Johannes J   Harris Tamara B TB   Heath Andrew C AC   Heikkilä Kauko K   Hofman Albert A   Homuth Georg G   Holliday Elizabeth G EG   Hopper John J   Hyppönen Elina E   Jacobsson Bo B   Jaddoe Vincent W V VW   Johannesson Magnus M   Jugessur Astanand A   Kähönen Mika M   Kajantie Eero E   Kardia Sharon L R SL   Keavney Bernard B   Kolcic Ivana I   Koponen Päivikki P   Kovacs Peter P   Kronenberg Florian F   Kutalik Zoltan Z   La Bianca Martina M   Lachance Genevieve G   Iacono William G WG   Lai Sandra S   Lehtimäki Terho T   Liewald David C DC   Lindgren Cecilia M CM   Liu Yongmei Y   Luben Robert R   Lucht Michael M   Luoto Riitta R   Magnus Per P   Magnusson Patrik K E PK   Martin Nicholas G NG   McGue Matt M   McQuillan Ruth R   Medland Sarah E SE   Meisinger Christa C   Mellström Dan D   Metspalu Andres A   Traglia Michela M   Milani Lili L   Mitchell Paul P   Montgomery Grant W GW   Mook-Kanamori Dennis D   de Mutsert Renée R   Nohr Ellen A EA   Ohlsson Claes C   Olsen Jørn J   Ong Ken K KK   Paternoster Lavinia L   Pattie Alison A   Penninx Brenda W J H BW   Perola Markus M   Peyser Patricia A PA   Pirastu Mario M   Polasek Ozren O   Power Chris C   Kaprio Jaakko J   Raffel Leslie J LJ   Räikkönen Katri K   Raitakari Olli O   Ridker Paul M PM   Ring Susan M SM   Roll Kathryn K   Rudan Igor I   Ruggiero Daniela D   Rujescu Dan D   Salomaa Veikko V   Schlessinger David D   Schmidt Helena H   Schmidt Reinhold R   Schupf Nicole N   Smit Johannes J   Sorice Rossella R   Spector Tim D TD   Starr John M JM   Stöckl Doris D   Strauch Konstantin K   Stumvoll Michael M   Swertz Morris A MA   Thorsteinsdottir Unnur U   Thurik A Roy AR   Timpson Nicholas J NJ   Tung Joyce Y JY   Uitterlinden André G AG   Vaccargiu Simona S   Viikari Jorma J   Vitart Veronique V   Völzke Henry H   Vollenweider Peter P   Vuckovic Dragana D   Waage Johannes J   Wagner Gert G GG   Wang Jie Jin JJ   Wareham Nicholas J NJ   Weir David R DR   Willemsen Gonneke G   Willeit Johann J   Wright Alan F AF   Zondervan Krina T KT   Stefansson Kari K   Krueger Robert F RF   Lee James J JJ   Benjamin Daniel J DJ   Cesarini David D   Koellinger Philipp D PD   den Hoed Marcel M   Snieder Harold H   Mills Melinda C MC  

Nature genetics 20161031 12


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 1  ...[more]

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