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Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus.

By Iain Mathieson, Felix R. Day, Nicola Barban, Felix C. Tropf, David M. Brazel, eQTLGen Consortium, BIOS Consortium, Ahmad Vaez, Natalie van Zuydam, Bárbara D. Bitarello, Harold Snieder, Marcel den Hoed, Ken K. Ong, Melinda C Mills, John R.B. Perry, on behalf of the Human Reproductive Behaviour Consortium

Posted 22 May 2020
bioRxiv DOI: 10.1101/2020.05.19.104455

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 Statement The authors have declared no competing interest.

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