Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.

Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

Barban, Nicola;
2021

Abstract

Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.
Mills, Melinda C.; Tropf, Felix C.; Brazel, David M.; van Zuydam, Natalie; Vaez, Ahmad; Agbessi, Mawussé; Ahsan, Habibul; Alves, Isabel; Andiappan, Anand Kumar; Arindrarto, Wibowo; Awadalla, Philip; Battle, Alexis; Beutner, Frank; Jan Bonder, Marc; Boomsma, Dorret I.; Christiansen, Mark W.; Claringbould, Annique; Deelen, Patrick; Esko, Tõnu; Favé, Marie-Julie; Franke, Lude; Frayling, Timothy; Gharib, Sina A.; Gibson, Greg; Heijmans, Bastiaan T.; Hemani, Gibran; Jansen, Rick; Kähönen, Mika; Kalnapenkis, Anette; Kasela, Silva; Kettunen, Johannes; Kim, Yungil; Kirsten, Holger; Kovacs, Peter; Krohn, Knut; Kronberg, Jaanika; Kukushkina, Viktorija; Kutalik, Zoltan; Lee, Bernett; Lehtimäki, Terho; Loeffler, Markus; Marigorta, Urko M.; Mei, Hailang; Milani, Lili; Montgomery, Grant W.; Müller-Nurasyid, Martina; Nauck, Matthias; Nivard, Michel G.; Penninx, Brenda W. J. H.; Perola, Markus; Pervjakova, Natalia; Pierce, Brandon L.; Powell, Joseph; Prokisch, Holger; Psaty, Bruce M.; Raitakari, Olli T.; Ripatti, Samuli; Rotzschke, Olaf; Rüeger, Sina; Saha, Ashis; Scholz, Markus; Schramm, Katharina; Seppälä, Ilkka; Slagboom, Eline P.; Stehouwer, Coen D. A.; Stumvoll, Michael; Sullivan, Patrick; ‘t Hoen, Peter A. C.; Teumer, Alexander; Thiery, Joachim; Tong, Lin; Tönjes, Anke; van Dongen, Jenny; van Iterson, Maarten; van Meurs, Joyce; Veldink, Jan H.; Verlouw, Joost; Visscher, Peter M.; Völker, Uwe; Võsa, Urmo; Westra, Harm-Jan; Wijmenga, Cisca; Yaghootkar, Hanieh; Yang, Jian; Zeng, Biao; Zhang, Futao; Heijmans, Bastiaan T.; ‘t Hoen, Peter A. C.; van Meurs, Joyce; Isaacs, Aaron; Jansen, Rick; Franke, Lude; Boomsma, Dorret I.; Pool, René; van Dongen, Jenny; Jan Hottenga, Jouke; van Greevenbroek, Marleen M. J.; Stehouwer, Coen D. A.; van der Kallen, Carla J. H.; Schalkwijk, Casper G.; Wijmenga, Cisca; Franke, Lude; Zhernakova, Sasha; Tigchelaar, Ettje F.; Slagboom, Eline P.; Beekman, Marian; Deelen, Joris; van Heemst, Diana; Veldink, Jan H.; van den Berg, Leonard H.; van Duijn, Cornelia M.; Hofman, Bert A.; Isaacs, Aaron; Uitterlinden, André G.; van Meurs, Joyce; Jhamai, P. Mila; Verbiest, Michael; Suchiman, H. Eka D.; Verkerk, Marijn; van der Breggen, Ruud; van Rooij, Jeroen; Lakenberg, Nico; Mei, Hailiang; van Iterson, Maarten; van Galen, Michiel; Bot, Jan; Zhernakova, Dasha V.; Jansen, Rick; van ’t Hof, Peter; Deelen, Patrick; Nooren, Irene; ‘t Hoen, Peter A. C.; Heijmans, Bastiaan T.; Moed, Matthijs; Franke, Lude; Vermaat, Martijn; Zhernakova, Dasha V.; Luijk, René; Jan Bonder, Marc; van Iterson, Maarten; Deelen, Patrick; van Dijk, Freerk; van Galen, Michiel; Arindrarto, Wibowo; Kielbasa, Szymon M.; Swertz, Morris A.; van Zwet, Erik. W.; Jansen, Rick; ‘t Hoen, Peter A. C.; Heijmans, Bastiaan T.; Akimova, Evelina T.; Bergmann, Sven; Boardman, Jason D.; Boomsma, Dorret I.; Brumat, Marco; Buring, Julie E.; Cesarini, David; Chasman, Daniel I.; Chavarro, Jorge E.; Cocca, Massimiliano; Concas, Maria Pina; Davey-Smith, George; Davies, Gail; Deary, Ian J.; Esko, Tõnu; Franco, Oscar; Gaskins, Audrey J.; de Geus, Eco J. C.; Gieger, Christian; Girotto, Giorgia; Grabe, Hans Jörgen; Gunderson, Erica P.; Harris, Kathleen Mullan; Hartwig, Fernando P.; He, Chunyan; van Heemst, Diana; Hill, W. David; Homuth, Georg; Horta, Bernando Lessa; Jan Hottenga, Jouke; Huang, Hongyang; Hyppӧnen, Elina; Ikram, M. Arfan; Jansen, Rick; Johannesson, Magnus; Kamali, Zoha; Kavousi, Maryam; Kraft, Peter; Kühnel, Brigitte; Langenberg, Claudia; Lind, Penelope A.; Luan, Jian’an; Mägi, Reedik; Magnusson, Patrik K. E.; Mahajan, Anubha; Martin, Nicholas G.; Mbarek, Hamdi; McCarthy, Mark I.; McMahon, George; McQueen, Matthew B.; Medland, Sarah E.; Meitinger, Thomas; Metspalu, Andres; Mihailov, Evelin; Milani, Lili; Missmer, Stacey A.; Møllegaard, Stine; Mook-Kanamori, Dennis O.; Morgan, Anna; van der Most, Peter J.; de Mutsert, Renée; Nauck, Matthias; Nolte, Ilja M.; Noordam, Raymond; Penninx, Brenda W. J. H.; Peters, Annette; Power, Chris; Redmond, Paul; Rich-Edwards, Janet W.; Ridker, Paul M.; Rietveld, Cornelius A.; Ring, Susan M.; Rose, Lynda M.; Rueedi, Rico; Stefánsson, Kári; Stöckl, Doris; Strauch, Konstantin; Swertz, Morris A.; Teumer, Alexander; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Turman, Constance; Uitterlinden, André G.; Waldenberger, Melanie; Wareham, Nicholas J.; Willemsen, Gonneke; Zhao, Jing Hau; Pers, Tune H.; Snieder, Harold; Perry, John R. B.; Ong, Ken K.; den Hoed, Marcel; Barban, Nicola; Day, Felix R.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/848362
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