TY - JOUR
T1 - Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
AU - eQTLgen Consortium
AU - BIOS Consortium
AU - Management Team
AU - Cohort collection
AU - Data Generation
AU - Data management and computational infrastructure
AU - Data Analysis Group
AU - Human Reproductive Behaviour Consortium
AU - LifeLines Cohort Study
AU - Mills, Melinda C.
AU - Tropf, Felix C.
AU - Brazel, David M.
AU - van Zuydam, Natalie
AU - Vaez, Ahmad
AU - Agbessi, Mawussé
AU - Ahsan, Habibul
AU - Alves, Isabel
AU - Andiappan, Anand Kumar
AU - Arindrarto, Wibowo
AU - Awadalla, Philip
AU - Battle, Alexis
AU - Beutner, Frank
AU - Jan Bonder, Marc
AU - Boomsma, Dorret I.
AU - Christiansen, Mark W.
AU - Claringbould, Annique
AU - Deelen, Patrick
AU - Esko, Tõnu
AU - Favé, Marie Julie
AU - Franke, Lude
AU - Frayling, Timothy
AU - Gharib, Sina A.
AU - Gibson, Greg
AU - Heijmans, Bastiaan T.
AU - Hemani, Gibran
AU - Jansen, Rick
AU - Kähönen, Mika
AU - Kalnapenkis, Anette
AU - Kasela, Silva
AU - Kettunen, Johannes
AU - Kim, Yungil
AU - Kirsten, Holger
AU - Kovacs, Peter
AU - Krohn, Knut
AU - Kronberg, Jaanika
AU - Kukushkina, Viktorija
AU - Kutalik, Zoltan
AU - Lee, Bernett
AU - Lehtimäki, Terho
AU - Loeffler, Markus
AU - Marigorta, Urko M.
AU - Mei, Hailang
AU - Milani, Lili
AU - Montgomery, Grant W.
AU - Müller-Nurasyid, Martina
AU - Nauck, Matthias
AU - Nivard, Michel G.
AU - Penninx, Brenda W.J.H.
AU - Cesarini, David
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Adolescent
KW - Age Factors
KW - Coitus/physiology
KW - Female
KW - Genetic Association Studies
KW - Humans
KW - Male
KW - Parturition/genetics
KW - Polymorphism, Single Nucleotide
KW - Reproduction/genetics
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UR - http://www.scopus.com/inward/citedby.url?scp=85117508270&partnerID=8YFLogxK
U2 - 10.1038/s41562-021-01135-3
DO - 10.1038/s41562-021-01135-3
M3 - Article
C2 - 34211149
AN - SCOPUS:85117508270
SN - 2397-3374
VL - 5
SP - 1717
EP - 1730
JO - Nature human behaviour
JF - Nature human behaviour
IS - 12
ER -