LAUSR

Mental disorders present a global health concern, with limited treatment options. In today's medical practice, medications such as antidepressants are prescribed not only for depression, but also for conditions such as anxiety and attention deficit hyperactivity disorder (ADHD). Therefore, identifying gene targets for specific disorders is important and offers improved precision. In this study, we performed a genetic analysis of six common mental disorders, ADHD, anxiety, depression, delays in mental developments, intellectual disabilities (ID), and speech/language disorder in the ethnic minority of African Americans (AA) using whole genome sequencing (WGS). WGS data was generated from blood-derived DNA from 4178 AA individuals, including 1384 patients with the diagnosis of at least one mental disorder. Mutation burden analysis was applied based on rare and deleterious mutations in the AA population between cases and controls, and further analyzed in the context of patients with single mental disorder diagnosis. Certain genes uncovered demonstrated significant p values in mutation burden analysis. In addition, exclusive recurrences in specific type of disorder were scanned through gene-drug interaction databases to assess for availability of potential medications. We uncovered 15 genes harboring deleterious mutations, including HMGCR and UST for ADHD; FNTB for anxiety, XIRP2, NPPC, , STK33, PANX1 and NTS for depression; RUNX3, TACR1, and NDUFS7 for delays in mental developments; HPN for ID; COL6A3, DDB1, and NDUFA11 for speech/language disorder. Taken together, we have established critical insight into the development of new precision medicine approaches for mental disorders in African Americans.