Identification of 370 loci for age at onset of sexual and reproductive behaviour, highlighting common aetiology with reproductive biology, externalizing behaviour and longevity

Mills, M. C.; Tropf, F. C.; Brazel, D. M.; van Zuydam, N.; Vaez, A.; eQTLGen Consortium,; BIOS Consortium,; Pers, T. H.; Snieder, H.; Perry, J. R. B.; Ong, K. K.; den Hoed, M.; Barban, N.; Day, F. R.; Human Reproductive Behaviour Consortium,

doi:10.1101/2020.05.06.081273

bioRxiv · 10.1101/2020.05.06.081273

Identification of 370 loci for age at onset of sexual and reproductive behaviour, highlighting common aetiology with reproductive biology, externalizing behaviour and longevity

Mills, M. C.·Tropf, F. C.·Brazel, D. M.·van Zuydam, N.·Vaez, A.·eQTLGen Consortium,·BIOS Consortium,·Pers, T. H.·Snieder, H.·Perry, J. R. B.·Ong, K. K.·den Hoed, M.·Barban, N.·Day, F. R.·Human Reproductive Behaviour Consortium,

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Abstract

Age at first sexual intercourse (AFS) and age at first birth (AFB) have implications for health and evolutionary fitness. In the largest genome-wide association study to date (AFS, N=387,338; AFB, N=542,901), we identify 370 independent signals, 11 sex-specific, with a 5-6% polygenic score (PGS) prediction. Heritability of AFB shifted from 9% [CI=4-14] for women born in 1940 to 22% [CI=19-25] 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. Polycystic Ovarian Syndrome leads to later AFB, linking with infertility. Late AFB is protective against later-life disease and associated with parental longevity. Higher childhood socioeconomic circumstances and those in the highest PGS decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, for understanding longevity, and guiding experimentation into mechanisms of infertility.

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Mills, M. C., Tropf, F. C., Brazel, D. M., van Zuydam, N., Vaez, A., eQTLGen Consortium,, BIOS Consortium,, Pers, T. H., Snieder, H., Perry, J. R. B., Ong, K. K., den Hoed, M., Barban, N., Day, F. R., Human Reproductive Behaviour Consortium,. 2020-05-07. Identification of 370 loci for age at onset of sexual and reproductive behaviour, highlighting common aetiology with reproductive biology, externalizing behaviour and longevity. https://doi.org/10.1101/2020.05.06.081273

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