%0 Journal Article %A Judit Cabana-Domínguez %A Anu Shivalikanjli %A Noèlia Fernàndez-Castillo %A Bru Cormand %T Genome-wide association meta-analysis of cocaine dependence: shared genetics with comorbid conditions %D 2018 %R 10.1101/374553 %J bioRxiv %P 374553 %X Cocaine dependence is a complex neuropsychiatric disorder that is highly comorbid with other psychiatric traits. Association studies suggest that common genetic variants contribute substantially to cocaine dependence susceptibility. Also, increasing evidence supports the role of shared genetic risk factors in the lifetime co-occurrence of psychiatric traits and cocaine dependence. Here we performed a genome-wide association study (GWAS) meta-analysis of cocaine dependence using four different dbGaP datasets (2,085 cases and 4,293 controls). Although no genome-wide significant hits were found in the SNP-based analysis, the gene-based analysis identified HIST1H2BD as significantly 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. The top SNPs of this region, rs806973 and rs56401801 (P=3.14e-06 and 3.44e-06, respectively), are eQTLs for different genes in multiple brain areas. Furthermore, we performed LD Score regression (LDSC) analysis with comorbid conditions and found significant genetic correlations between cocaine dependence and ADHD, SCZ, MDD and risk-taking behavior. We also found, through polygenic risk score (PRS) analysis, that all tested phenotypes can significantly predict cocaine dependence status: SCZ (R2=2.28%; P=1.21e-26), ADHD (R2=1.39%; P=4.5e-17), risk-taking behavior (R2=0.60%; P=2.7e-08), MDD (R2=1.21%; P=4.35e-15), children’s aggressive behavior (R2=0.3%; P=8.8e-05) and antisocial behavior (R2=1.33%; P=2.2e-16). To our knowledge, this is the largest reported cocaine dependence GWAS meta-analysis on European ancestry individuals. Despite the small sample size, we identified suggestive associations in regions that may be related to cocaine dependence. Furthermore, we found evidence for shared genetic risk factors between cocaine dependence and several comorbid psychiatric traits. %U https://www.biorxiv.org/content/biorxiv/early/2018/07/23/374553.full.pdf