An atlas of genetic correlations between gestational age and common psychiatric disorders.

Abstract

We aim to systematically explore the potential genetic correlations between five major psychiatric disorders and gestational ages. Genome-wide association study (GWAS) summary datasets of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) in discovery were downloaded from the Psychiatric GWAS Consortium (PGC) website. Suggestive (Raw p < 0.05) genetic associations in the discovery phrase were further replicated in independent GWASs which downloaded from PGC, the FinnGen study or Integrative Psychiatric Research (iPSYCH) website. GWASs of gestational duration, preterm and post-term birth were derived from previous studies of infants from the Early Growth Genetics (EGG) Consortium, the iPSYCH study, and the Genomic and Proteomic Network for Preterm Birth Research (GPN). We calculated genetic correlations using linkage disequilibrium score (LDSC) regression. Mendelian randomization (MR) analyses were performed to investigate the causal effects. We identified four suggestive genetic correlations between psychiatric disorders and gestational age factors in discovery LDSC and two replicated in a confirmation LDSC: gestational duration and ADHD (rg =-0.1405, FDR p=0.0406), post-term birth and SCZ (rg =-0.2003, FDR p=0.0042). We also observed causal effect of post-term birth on SCZ by MR (PWeighted median =0.037, PInverse variance weighted =0.007). Our analysis suggested no significant evidence of horizontal pleiotropy and heterogeneity. This study showed the genetic correlation evidences between gestational age phenotypes and psychiatric disorders, providing novel clues for understanding the pathogenic factors of common psychiatric disorders. LAY SUMMARY: Whereas gestational age factors were reported to be associated with psychiatric disorders, the genetic relationship and causality remain to be revealed. The present study reported the first large-scale genetic correlations investigation of the associations between gestational age phenotypes and psychiatric disorders. Results indicate causal relationships between post-term birth and schizophrenia (SCZ), as well as suggestive genetic correlations between gestational duration and attention deficit/hyperactivity disorder (ADHD). This study provided novel clues for understanding the pathogenic factors of common psychiatric disorders.