Genome-wide association meta-analysis of cocaine dependence: Shared genetics with comorbid conditions

Publication date: Available online 15 June 2019Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Judit Cabana-Domínguez, Anu Shivalikanjli, Noèlia Fernàndez-Castillo, Bru CormandAbstractCocaine dependence is a complex psychiatric disorder that is highly comorbid with other psychiatric traits. Twin and adoption studies suggest that genetic variants contribute substantially to cocaine dependence susceptibility, which has an estimated heritability of 65–79%. Here we performed a meta-analysis of genome-wide association studies of cocaine dependence using four datasets from the dbGaP repository (2085 cases and 4293 controls, all of them selected by their European ancestry). Although no genome-wide significant hits were found in the SNP-based analysis, the gene-based analysis identified HIST1H2BD as associated with cocaine-dependence (10% FDR). This gene is located in a region on chromosome 6 enriched in histone-related genes, previously associated with schizophrenia (SCZ). Furthermore, we performed LD Score regression analysis with comorbid conditions and found significant genetic correlations between cocaine dependence and SCZ, ADHD, major depressive disorder (MDD) and risk taking. We also found, through polygenic risk score analysis, that all tested phenotypes are significantly associated with cocaine dependence status: SCZ (R2 = 2.28%; P = 1.21e-26), ADHD (R2 = 1.39%; P = 4.5e-17), risk taking (R2 = 0.60%; P = 2.7e-08)...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research