title: Genome-Wide Association of Heroin Dependence in Han Chinese.
abstract: 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.
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, MRC SGDP Centre, King's College London, United Kingdom.
authors.forename: Gursharan
authors.identifier: http://orcid.org/0000-0002-5156-7176
authors.initials: G
authors.lastname: Kalsi
authors.affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
authors.forename: Jack
authors.initials: J
authors.lastname: Euesden
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, MRC SGDP Centre, King's College London, United Kingdom.
authors.forename: Jonathan R I
authors.initials: JR
authors.lastname: Coleman
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, MRC SGDP Centre, King's College London, United Kingdom.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ducci
authors.affiliation: Department of Actuarial Sciences and Risk Management, Faculty of Business, Karabuk University, Karabuk, Turkey.
authors.forename: Fazil
authors.initials: F
authors.lastname: Aliev
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, MRC SGDP Centre, King's College London, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Newhouse
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Sichuan, People's Republic of China.|Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, People's Republic of China.
authors.forename: Xiehe
authors.initials: X
authors.lastname: Liu
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Sichuan, People's Republic of China.|Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Ma
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Sichuan, People's Republic of China.|Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan, People's Republic of China.
authors.forename: Yingcheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, MRC SGDP Centre, King's College London, United Kingdom.|Lilly UK, Erl Wood Manor, Windlesham, Surrey, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, MRC SGDP Centre, King's College London, United Kingdom.
authors.forename: Philip
authors.initials: P
authors.lastname: Asherson
authors.affiliation: Department of Psychiatry, West China Hospital, School of Medicine, Sichuan University, Sichuan, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, MRC SGDP Centre, King's College London, United Kingdom.
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006556:Heroin Dependence / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D064067:Rho Guanine Nucleotide Exchange Factors / Q000235:genetics
chemical_list: C577232:ARHGEF10 protein, human; D064067:Rho Guanine Nucleotide Exchange Factors; C507732:Brsk2 protein, human; D017346:Protein Serine-Threonine Kinases