Psychiatric Genome-wide Association Study Enrichment Shows Promise for Future Psychopharmaceutical Discoveries

Abstract

Innovation in psychiatric therapeutics has stagnated on a handful of known mechanisms. Psychiatric genome-wide association studies (GWASs) have begun to identify hundreds of genome-wide significant (GWS) loci and characterize complex polygenic architectures. These data have rapidly advanced our understanding of disease etiology but their ability to inform clinical treatment in psychiatry remains largely unexplored. Here, we show that large psychiatric GWASs (schizophrenia, bipolar disorder, major depressive disorder, and substance use disorders) are enriched (OR: 2.776-27.629) for drug targets of current therapeutics used to treat these disorders (e.g., SNRI’s for MDD; antipsychotics for schizophrenia and MDD). The effect sizes of individual loci and the number of variants identified in a study, but not functional annotations of SNPs, drove enrichment. Psychiatric GWAS results may assist in drug repurposing and novel treatment identification.