The genetic relationship between female reproductive traits and six psychiatric disorders

Guiyan Ni,S Hong Lee,Xuan Zhou,Jacob Gratten,Natalie Mills,Azmeraw T Amare

doi:10.1038/s41598-019-48403-x

Abstract

Female reproductive behaviours have important implications for evolutionary fitness and health of offspring. Here we used the second release of UK Biobank data (N = 220,685) to evaluate the association between five female reproductive traits and polygenic 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 age at first birth (AFB) (genetic correlation of −0.68 ± 0.03), age at first sexual intercourse (AFS) (−0.56 ± 0.03), number of live births (NLB) (0.36 ± 0.04) and age at menopause (−0.27 ± 0.04). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (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 schizophrenia and AFS (−0.10 ± 0.03). These associations were mostly explained by pleiotropic effects and there was little evidence of causal relationships. Our findings can potentially help improve reproductive health in women, hence better child outcomes. Our findings also lend partial support to the evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success.

Highlights

Female reproductive behaviours, including age at first birth (AFB), age at first sexual intercourse (AFS), age at menarche (AMC), age at menopause (AMP) and number of live births (NLB) have important implications in reproductive health and evolutionary fitness[1,2]
We investigate the genetic association of five specific reproductive traits in women (AFB, AFS, AMC, AMP and NLB) with six common psychiatric disorders (ADHD, autism spectrum disorder (ASD), eating disorders (ED), bipolar disorder (BIP), major depressive disorder (MDD), and SCZ) using polygenic score and linkage disequilibrium score regression (LDSC) approach
The total sample of women was divided into five groups according to their AFB, AFS, AMC, AMP or NLB status (Table 1) to detect the mean difference of polygenic risk scores (PRS) across the five categories

Summary

Introduction

Female reproductive behaviours, including age at first birth (AFB), age at first sexual intercourse (AFS), age at menarche (AMC), age at menopause (AMP) and number of live births (NLB) have important implications in reproductive health and evolutionary fitness[1,2]. Some of these traits have been shown to associate with the physical and mental health of offspring[3], and there has been growing evidence that maternal AFB is associated with increased risk of psychiatric disorder[4,5] and behavioural problems in their children[6,7]. This study provides insight into whether complex phenotypes of reproductive behaviour can be caused by mental health or rather by pleiotropic genes associated with both traits

Methods

Results

Conclusion