Genome-Wide Association of Heroin Dependence in Han Chinese

• Published in: PloS one Vol. 11; no. 12; p. e0167388
• Main Authors: Kalsi, Gursharan, Euesden, Jack, Coleman, Jonathan R. I., Ducci, Francesca, Aliev, Fazil, Newhouse, Stephen J., Liu, Xiehe, Ma, Xiaohong, Wang, Yingcheng, Collier, David A., Asherson, Philip, Li, Tao, Breen, Gerome
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.12.2016; Public Library of Science (PLoS)
• Subjects: Adult; Asian People - genetics; Association analysis; Biology and Life Sciences; Biomarkers; China - epidemiology; Chromosome 20; Chromosome 8; Diagnostic systems; Dopamine; Drug abuse; Drug addiction; Female; Gene Frequency; Genes; Genetic aspects; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotypes; Guanine; Guanine nucleotide exchange factor; Han (Chinese people); Health aspects; Health care; Heroin; Heroin Dependence - epidemiology; Heroin Dependence - genetics; Humans; Hypotheses; Laboratories; Linkage Disequilibrium; Male; Medicine and Health Sciences; Mental disorders; Mental health; Narcotics; Neurosciences; People and places; Polymorphism, Genetic; Protein Serine-Threonine Kinases - genetics; Psychiatry; Rho Guanine Nucleotide Exchange Factors - genetics; Risk analysis; Risk factors; Risk sharing; Schizophrenia; Serine; Social Sciences; Substance abuse; Threonine; Tobacco; China; United Kingdom > UK
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167388

Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110-6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field.