Genome-wide analyses reveal novel opioid use disorder loci and genetic overlap with schizophrenia, bipolar disorder, and major depression (original) (raw)

Opioid use disorder (OUD) and mental disorders are often comorbid, with increased morbidity and mortality. The causes underlying this relationship are poorly understood. Although these conditions are highly heritable, their shared genetic vulnerabilities remain unaccounted for. We applied the conditional/conjunctional false discovery rate (cond/conjFDR) approach to analyse summary statistics from independent genome wide association studies of OUD, SCZ, BD and MD. Next, we characterized the identified shared loci using biological annotation resources. OUD data was obtained from the Million Veteran Program (15,756 cases 99,039 controls). SCZ (53,386 cases 77,258 controls), BD (41,917 cases 371,549 controls) and MD (170,756 cases 329,443 controls) data was provided by the Psychiatric Genomics Consortium. We discovered genetic enrichment for OUD conditional on associations with SCZ, BD, MD and vice versa, indicating polygenic overlap with identification of 14 novel OUD loci at condFDR&l...