Age at first birth in women is genetically associated with increased risk of schizophrenia

ABSTRACT Previous studies have shown an increased risk for a range of mental health issues in children born to both younger and older parents compared to children of average-aged parents. However, until recently, it was not clear if these increased risks are due to psychosocial factors associated with age or if parents at higher genetic risk for psychiatric disorders tend to have children at an earlier or later age. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age of mothers at the birth of their first child (AFB). Here, we use independent data from the UK Biobank (N=38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, end to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value=1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value=3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE=0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE=0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.