RT Journal Article SR Electronic T1 Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.19.104455 DO 10.1101/2020.05.19.104455 A1 Iain Mathieson A1 Felix R. Day A1 Nicola Barban A1 Felix C. Tropf A1 David M. Brazel A1 eQTLGen Consortium A1 BIOS Consortium A1 Ahmad Vaez A1 Natalie van Zuydam A1 Bárbara D. Bitarello A1 Harold Snieder A1 Marcel den Hoed A1 Ken K. Ong A1 Melinda C. Mills A1 John R.B. Perry A1 on behalf of the Human Reproductive Behaviour Consortium YR 2020 UL http://biorxiv.org/content/early/2020/05/22/2020.05.19.104455.abstract AB Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and also identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identify 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology across the life course, including puberty timing, age at first birth, sex hormone regulation and age at menopause. Missense alleles in ARHGAP27 were associated with increased NEB but reduced reproductive lifespan, suggesting a trade-off between reproductive ageing and intensity. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Accordingly, we find that NEB-increasing alleles have increased in frequency over the past two generations. Furthermore, integration with data from ancient selection scans identifies a unique example of an allele—FADS1/2 gene locus—that has been under selection for thousands of years and remains under selection today. Collectively, our findings demonstrate that diverse biological mechanisms contribute to reproductive success, implicating both neuro-endocrine and behavioural influences.Competing Interest StatementThe authors have declared no competing interest.