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.
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Our policy is to make genome-wide summary statistics widely and publically available. Upon publication, summary statistics will be available on the GWAS catalogue website: https://www.ebi.ac.uk/gwas/downloads/summary-statistics.
The phenotype and genotype data for separate studies used in this GWAS are available upon application to each of the participating cohorts, who can be contacted directly to follow their different data access policies. Access to the UK Biobank is available through application with information available at: http://www.ukbiobank.ac.uk.
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A detailed list of funding and other acknowledgements for each cohort can be found in Supplementary Sect. 14. This research was conducted using the UK Biobank resource under application 22276 and 9905. Funding was provided to M.C.M. by the ERC, SOCIOGENOME (615603), CHRONO (835079), ESRC/UKRI SOCGEN (ES/N011856/1), Wellcome Trust ISSF, Leverhulme Trust and Leverhulme Centre for Demographic Science, to N.B. by ERC GENPOP (865356), to F.C.T. by LabEx Ecode, French National Research Agency (ANR) Investissements d’Avenir (ANR-11-LABX-0047), to M.d.H. by Swedish Heart-Lung Foundation (20170872, 20200781, 20140543, 20170678, 20180706 and 20200602), Kjell and Märta Beijer Foundation and Swedish Research Council (2015-03657, 2019-01417). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This study received ethical approval from the Department of Sociology, University of Oxford, and relevant ethical approval was obtained at the local level for the contributing datasets. The authors thank E. T. Akimova and S. Møllegaard for administrative work in the organization of the cohort information and author list.
The main authors declare no competing interests. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.I.M. has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier and Takeda. As of June 2019, M.I.M. is an employee of Genentech and a holder of Roche stock.
Peer review information Nature Human Behaviour thanks Ahmed Elhakeem and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Mills, M.C., Tropf, F.C., Brazel, D.M. et al. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour. Nat Hum Behav (2021). https://doi.org/10.1038/s41562-021-01135-3