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.
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
Overview publication
| Title | Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour. |
| Date | December 1st, 2021 |
| Issue name | Nature human behaviour |
| Issue number | v5.12:1717-1730 |
| DOI | 10.1038/s41562-021-01135-3 |
| Authors | |
| Info | Agbessi M, Ahsan H, Alves I, Andiappan AK, Arindrarto W, Awadalla P, Battle A, Beutner F, Jan Bonder M, Boomsma DI, Christiansen MW, Claringbould A, Deelen P, Esko T, Favé MJ, Franke L, Frayling T, Gharib SA, Gibson G, Heijmans BT, Hemani G, Jansen R, Kähönen M, Kalnapenkis A, Kasela S, Kettunen J, Kim Y, Kirsten H, Kovacs P, Krohn K, Kronberg J, Kukushkina V, Kutalik Z, Lee B, Lehtimäki T, Loeffler M, Marigorta UM, Mei H, Milani L, Montgomery GW, Müller-Nurasyid M, Nauck M, Nivard MG, Penninx BWJH, Perola M, Pervjakova N, Pierce BL, Powell J, Prokisch H, Psaty BM, Raitakari OT, Ripatti S, Rotzschke O, Rüeger S, Saha A, Scholz M, Schramm K, Seppälä I, Slagboom EP, Stehouwer CDA, Stumvoll M, Sullivan P, 't Hoen PAC, Teumer A, Thiery J, Tong L, Tönjes A, van Dongen J, van Iterson M, van Meurs J, Veldink JH, Verlouw J, Visscher PM, Völker U, Võsa U, Westra HJ, Wijmenga C, Yaghootkar H, Yang J, Zeng B, Zhang F, Heijmans BT, 't Hoen PAC, van Meurs J, Isaacs A, Jansen R, Franke L, Boomsma DI, Pool R, van Dongen J, Jan Hottenga J, van Greevenbroek MMJ, Stehouwer CDA, van der Kallen CJH, Schalkwijk CG, Wijmenga C, Franke L, Zhernakova S, Tigchelaar EF, Slagboom EP, Beekman M, Deelen J, van Heemst D, Veldink JH, van den Berg LH, van Duijn CM, Hofman BA, Isaacs A, Uitterlinden AG, van Meurs J, Jhamai PM, Verbiest M, Suchiman HED, Verkerk M, van der Breggen R, van Rooij J, Lakenberg N, Mei H, van Iterson M, van Galen M, Bot J, Zhernakova DV, Jansen R, van 't Hof P, Deelen P, Nooren I, 't Hoen PAC, Heijmans BT, Moed M, Franke L, Vermaat M, Zhernakova DV, Luijk R, Jan Bonder M, van Iterson M, Deelen P, van Dijk F, van Galen M, Arindrarto W, Kielbasa SM, Swertz MA, van Zwet EW, Jansen R, 't Hoen PAC, Heijmans BT, Akimova ET, Bergmann S, Boardman JD, Boomsma DI, Brumat M, Buring JE, Cesarini D, Chasman DI, Chavarro JE, Cocca M, Concas MP, Davey-Smith G, Davies G, Deary IJ, Esko T, Franco O, Gaskins AJ, de Geus EJC, Gieger C, Girotto G, Grabe HJ, Gunderson EP, Harris KM, Hartwig FP, He C, van Heemst D, Hill WD, Homuth G, Horta BL, Jan Hottenga J, Huang H, Hyppӧnen E, Ikram MA, Jansen R, Johannesson M, Kamali Z, Kavousi M, Kraft P, Kühnel B, Langenberg C, Lind PA, Luan J, Mägi R, Magnusson PKE, Mahajan A, Martin NG, Mbarek H, McCarthy MI, McMahon G, McQueen MB, Medland SE, Meitinger T, Metspalu A, Mihailov E, Milani L, Missmer SA, Møllegaard S, Mook-Kanamori DO, Morgan A, van der Most PJ, de Mutsert R, Nauck M, Nolte IM, Noordam R, Penninx BWJH, Peters A, Power C, Redmond P, Rich-Edwards JW, Ridker PM, Rietveld CA, Ring SM, Rose LM, Rueedi R, Stefánsson K, Stöckl D, Strauch K, Swertz MA, Teumer A, Thorleifsson G, Thorsteinsdottir U, Thurik AR, Timpson NJ, Turman C, Uitterlinden AG, Waldenberger M, Wareham NJ, Willemsen G, Zhao JH |
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