This study represents the largest and most inclusive GWAS of MD to date, identifying 697 independent SNP associations located within 635 independent genetic loci and evidence that neuronal differentiation and receptor clustering are involved in the etiology of the disorder. 308 high-confidence gene associations were identified (summarized in Table S8) in European ancestries. There was convergent evidence from multiple approaches for 15 genes, such as CYP7B1, a gene encoding a cytochrome P450 enzyme involved in neurosteroid synthesis. However, the results of each gene prioritization approach were largely distinct, potentially representing the differential sensitivity of each approach to variants within (fine-mapping) or outside (regulatory) gene boundaries. Results from conventional gene-association and chromatin interaction mapping approaches also implicated DRD2 involvement in MD. Previous work has shown that DRD2 inhibition suppresses neuroinflammation in mice,23 supporting a potentially testable mechanism linking genetic variation to MD.
