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The genetic relationship between female reproductive traits and six psychiatric disorders

By Guiyan Ni, Azmeraw Amare, Xuan Zhou, Natalie Mills, Jacob Gratten, Sang Hong Lee

Posted 03 Oct 2018
bioRxiv DOI: 10.1101/433946 (published DOI: 10.1038/s41598-019-48403-x)

Female reproductive behaviors have an important implication in evolutionary fitness and health of offspring. Previous studies have shown that age at first birth of women (AFB) is genetically associated with schizophrenia (SCZ). However, for most other psychiatric disorders and reproductive traits, the latent shared genetic architecture is largely unknown. Here we used the second wave of UK Biobank data (N=220,685) to evaluate the association between five female reproductive traits and polygenetic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N=429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with AFB (genetic correlation of -0.68 +/- 0.03 with p-value = 1.86E-89), age at first sexual intercourse (AFS) (-0.56 +/- 0.03 with p-value = 3.42E-60), number of live births (NLB) (0.36 +/- 0.04 with p-value = 4.01E-17) and age at menopause (-0.27 +/- 0.04 with p-value = 5.71E-13). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (genetic correlation of 0.35 +/- 0.06), ED and AFS (0.19 +/- 0.06), Major depressive disorder (MDD) and AFB (-0.27 +/- 0.07), MDD and AFS (-0.27 +/- 0.03) and SCZ and AFS (-0.10 +/- 0.03). Our findings reveal the shared genetic architecture between the five reproductive traits in women and six psychiatric disorders, which have a potential implication that helps to improve reproductive health in women, hence better child outcomes. Our findings may also explain, at least in part, an evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success.

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