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

Research output: Contribution to journalJournal articlepeer-review

  • Melinda C. Mills
  • Felix C. Tropf
  • David M. Brazel
  • Natalie van Zuydam
  • Ahmad Vaez
  • Mawussé Agbessi
  • Habibul Ahsan
  • Isabel Alves
  • Anand Kumar Andiappan
  • Wibowo Arindrarto
  • Philip Awadalla
  • Alexis Battle
  • Frank Beutner
  • Marc Jan Bonder
  • Dorret I. Boomsma
  • Mark W. Christiansen
  • Annique Claringbould
  • Patrick Deelen
  • Tõnu Esko
  • Marie-Julie Favé
  • Lude Franke
  • Timothy Frayling
  • Sina A. Gharib
  • Greg Gibson
  • Bastiaan T. Heijmans
  • Gibran Hemani
  • Rick Jansen
  • Mika Kähönen
  • Anette Kalnapenkis
  • Silva Kasela
  • Johannes Kettunen
  • Yungil Kim
  • Holger Kirsten
  • Knut Krohn
  • Jaanika Kronberg
  • Viktorija Kukushkina
  • Zoltan Kutalik
  • Bernett Lee
  • Terho Lehtimäki
  • Markus Loeffler
  • Urko M. Marigorta
  • Hailang Mei
  • Lili Milani
  • Grant W. Montgomery
  • Martina Müller-Nurasyid
  • Matthias Nauck
  • Michel G. Nivard
  • Brenda W. J. H. Penninx
  • Møllegaard, Stine
  • Pers, Tune H
  • eQTLGen Consortium
  • BIOS Consortium
  • Human Reproductive Behaviour Consortium
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.
Original languageEnglish
JournalNature Human Behaviour
Pages (from-to)1717-1730
Publication statusPublished - 2021

ID: 273377635