4.7 Article

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

Journal

NATURE HUMAN BEHAVIOUR
Volume -, Issue -, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41562-021-01135-3

Keywords

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Funding

  1. ERC, SOCIOGENOME [615603]
  2. CHRONO [835079]
  3. ESRC/UKRI SOCGEN [ES/N011856/1]
  4. Wellcome Trust ISSF
  5. Leverhulme Trust
  6. Leverhulme Centre for Demographic Science
  7. ERC GENPOP [865356]
  8. LabEx Ecode, French National Research Agency (ANR) Investissements d'Avenir [ANR11-LABX-0047]
  9. Swedish Heart-Lung Foundation [20170872, 20200781, 20140543, 20170678, 20180706, 20200602]
  10. Kjell and Marta Beijer Foundation
  11. Swedish Research Council [2015-03657, 2019-01417]
  12. Swedish Research Council [2015-03657, 2019-01417] Funding Source: Swedish Research Council
  13. Swedish Heart-Lung Foundation [20200781, 20180706, 20200602] Funding Source: Swedish Heart-Lung Foundation
  14. European Research Council (ERC) [615603, 865356] Funding Source: European Research Council (ERC)

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This study on age of first sexual intercourse and first birth reveals 371 genetic signals, driven by reproductive biology, externalizing behavior, and environmental effects. Later reproductive onset is associated with lower incidence of some diseases, while early reproductive age is linked to lower genetic scores and childhood socioeconomic status.
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. This genome-wide study of age at first sexual intercourse and first birth identifies 371 signals driven by reproductive biology, externalising behaviour and environmental effects, with later onset associated with lower incidence of some diseases.

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