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

Melinda C. Mills (), Felix C. Tropf, David M. Brazel, Natalie Zuydam, Ahmad Vaez, Tune H. Pers, Harold Snieder, John R. B. Perry, Ken K. Ong, Marcel Hoed, Nicola Barban and Felix R. Day ()
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Melinda C. Mills: University of Oxford
Felix C. Tropf: University of Oxford
David M. Brazel: University of Oxford
Natalie Zuydam: Uppsala University and SciLifeLab
Ahmad Vaez: University of Groningen, University Medical Center Groningen
Tune H. Pers: University of Copenhagen
Harold Snieder: University of Groningen, University Medical Center Groningen
John R. B. Perry: University of Cambridge
Ken K. Ong: University of Cambridge
Marcel Hoed: Uppsala University and SciLifeLab
Nicola Barban: University of Bologna
Felix R. Day: University of Cambridge

Nature Human Behaviour, 2021, vol. 5, issue 12, 1717-1730

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41562-021-01135-3

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