Investigation of genetic loci shared between bipolar disorder and risk-taking propensity: potential implications for pharmacological interventions.

摘要: Patients with bipolar disorder (BD) often show increased risk-taking propensity, which may contribute to poor clinical outcome. While these two phenotypes are genetically correlated, there is scarce knowledge on the shared genetic determinants. Using GWAS datasets BD (41,917 cases and 371,549 controls) (n = 466,571), we dissected determinants using conjunctional false discovery rate (conjFDR) local covariance analysis. We investigated specificity of identified targets schizophrenia (SCZ) attention-deficit hyperactivity (ADHD). The putative functional role was evaluated different tools GTEx v. 8. Target druggability DGIdb enrichment for drug genome REPositioning drugs (GREP). Among 102 loci between risk-taking, 87% showed same direction effect. Sixty-two were specifically propensity BD, while others also either SCZ or ADHD. By leveraging pleiotropic enrichment, reported 15 novel specific associated 22 risk-taking. cross-disorder genes, CACNA1C (a known target calcium channel blockers) significantly both conjFDR (p = 0.001 both) as well analysis, predicted be differentially expressed in cerebellar hemisphere an eQTL-informed gene-based analysis (BD, Z = 7.48, p = 3.8E-14; risk-taking: Z = 4.66, p = 1.6E-06). first time propensity. Further investigation into blockers development innovative ligands channels might form basis pharmacotherapy patients