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

Iain Mathieson, Felix Day, Nicola Barban, Felix Tropf, David Brazel, Ahmad Vaez, Natalie van Zuydam, Barbara Bitarello, Harold Snieder, Marcel den Hoed, Ken Ong, Melinda Mills (+4 others)
2020 biorxiv/medrxiv   pre-print
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
more » ... leles 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.
doi:10.1101/2020.05.19.104455 fatcat:6tr3htztjvgt5n6gpjdvuayc3m