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Physical and neurobehavioral determinants of reproductive onset and success

Abstract

The ages of puberty, first sexual intercourse and first birth signify the onset of reproductive ability, behavior and success, respectively. In a genome-wide association study of 125,667 UK Biobank participants, we identify 38 loci associated (P < 5 × 10−8) with age at first sexual intercourse. These findings were taken forward in 241,910 men and women from Iceland and 20,187 women from the Women's Genome Health Study. Several of the identified loci also exhibit associations (P < 5 × 10−8) with other reproductive and behavioral traits, including age at first birth (variants in or near ESR1 and RBM6SEMA3F), number of children (CADM2 and ESR1), irritable temperament (MSRA) and risk-taking propensity (CADM2). Mendelian randomization analyses infer causal influences of earlier puberty timing on earlier first sexual intercourse, earlier first birth and lower educational attainment. In turn, likely causal consequences of earlier first sexual intercourse include reproductive, educational, psychiatric and cardiometabolic outcomes.

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Figure 1: Bar chart of genetic correlations for age at first sexual intercourse.
Figure 2: Manhattan plot of the GWAS for age at first sexual intercourse.
Figure 3: Cluster plot displaying associations between the 38 lead SNPs for age at first sexual intercourse and 15 other behavioral, reproductive and health-related traits in the UK Biobank study.

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Acknowledgements

This research has been conducted using the UK Biobank Resource. This work was supported by the Medical Research Council (Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2).

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All authors had full access to all of the data and take responsibility for the integrity of the data and the accuracy of the data analysis. F.R.D., P.M.R., K.S., K.K.O. and J.R.B.P. designed the studies. R.A.S., A.H., A.K., G.M., O.T.M., D.G., U.T. and J.E.B. were responsible for collection and generation of data. F.R.D., H.H., D.I.C., L.M.R., P.-R.L., P.S. and J.R.B.P. performed the statistical analysis; all authors contributed to the interpretation of the findings. F.R.D., K.K.O. and J.R.B.P. drafted the manuscript; all authors contributed to the final version.

Corresponding authors

Correspondence to Ken K Ong or John R B Perry.

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Day, F., Helgason, H., Chasman, D. et al. Physical and neurobehavioral determinants of reproductive onset and success. Nat Genet 48, 617–623 (2016). https://doi.org/10.1038/ng.3551

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