Investigating the shared genetic architecture between schizophrenia and obesity

Abstract

AbstractEvidence for reciprocal comorbidity of schizophrenia (SCZ) and obesity (OB) has grown in recent years. However, little is known regarding the shared genetic architecture or causality underlying the phenotypic association between SCZ and OB. Leveraging summary statistics from the hitherto largest genome-wide association study (GWAS) on each trait, we investigated the genetic overlap and causal associations of SCZ with OB. Our study demonstrated a genetic correlation between SCZ and OB, and the correlation was more evident in local genomic regions. The cross-trait meta-analysis identified 27 significant SNPs shared between SCZ and OB, most of which had the same direction of influence on both diseases. Mendelian randomization analysis showed a causal association of SCZ with OB, but not vice versa. Combining the gene expression information, we found that the genetic correlation between SCZ and OB is enriched in six regions of brain, led by the brain frontal cortex, and within these regions 34 functional genes were found to have an impact on both SCZ and OB. Taken together, our comprehensive genome-wide cross-trait analysis suggests a shared genetic basis including pleiotropic loci, tissue enrichment, and shared function genes between SCZ and OB. This work provides novel insights into the intrinsic genetic overlap of SCZ and OB, and highlights new opportunities and avenues for future investigation.