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

Author

Listed:
  • Melinda C. Mills

    (University of Oxford
    University of Oxford)

  • Felix C. Tropf

    (University of Oxford
    University of Oxford
    École Nationale de la Statistique et de L’administration Économique (ENSAE)
    Center for Research in Economics and Statistics (CREST))

  • David M. Brazel

    (University of Oxford
    University of Oxford)

  • Natalie Zuydam

    (Uppsala University and SciLifeLab)

  • Ahmad Vaez

    (University of Groningen, University Medical Center Groningen
    Isfahan University of Medical Sciences)

  • Tune H. Pers

    (University of Copenhagen
    Statens Serum Institut)

  • 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)

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.

Suggested Citation

  • 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 & Felix R. Day, 2021. "Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour," Nature Human Behaviour, Nature, vol. 5(12), pages 1717-1730, December.
    • Handle: RePEc:nat:nathum:v:5:y:2021:i:12:d:10.1038_s41562-021-01135-3
    DOI: 10.1038/s41562-021-01135-3
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    Cited by:

    1. Aoxing Liu & Evelina T. Akimova & Xuejie Ding & Sakari Jukarainen & Pekka Vartiainen & Tuomo Kiiskinen & Sara Koskelainen & Aki S. Havulinna & Mika Gissler & Stefano Lombardi & Tove Fall & Melinda C. , 2024. "Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women," Nature Human Behaviour, Nature, vol. 8(2), pages 276-287, February.
    2. Zhang, Yan & Fletcher, Jason & Lu, Qiongshi & Song, Jie, 2023. "Gender differences in the association between parity and cognitive function: Evidence from the UK biobank," Social Science & Medicine, Elsevier, vol. 320(C).
    3. Jasmin Wertz & Terrie E. Moffitt & Louise Arseneault & J. C. Barnes & Michel Boivin & David L. Corcoran & Andrea Danese & Robert J. Hancox & HonaLee Harrington & Renate M. Houts & Stephanie Langevin &, 2023. "Genetic associations with parental investment from conception to wealth inheritance in six cohorts," Nature Human Behaviour, Nature, vol. 7(8), pages 1388-1401, August.

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