title: ZNF804A variants confer risk for heroin addiction and affect decision making and gray matter volume in heroin abusers.
abstract: Drug addiction shares common neurobiological pathways and risk genes with other psychiatric diseases, including psychosis. One of the commonly identified risk genes associated with broad psychosis has been ZNF804A. We sought to test whether psychosis risk variants in ZNF804A increase the risk of heroin addiction by modulating neurocognitive performance and gray matter volume (GMV) in heroin addiction. Using case-control genetic analysis, we compared the distribution of ZNF804A variants (genotype and haplotype) in 1035 heroin abusers and 2887 healthy subjects. We also compared neurocognitive performance (impulsivity, global cognitive ability and decision-making ability) in 224 subjects and GMV in 154 subjects based on the ZNF804A variants. We found significant differences in the distribution of ZNF804A intronic variants (rs1344706 and rs7597593) allele and haplotype frequencies between the heroin and control groups. Decision-making impairment was worse in heroin abusers who carried the ZNF804A risk allele and haplotype. Subjects who carried more risk alleles and haplotypes of ZNF804A had greater GMV in the bilateral insular cortex, right temporal cortex and superior parietal cortex. The interaction between heroin addiction and ZNF804A variants affected GMV in the left sensorimotor cortex. Our findings revealed several ZNF804A variants that were significantly associated with the risk of heroin addiction, and these variants affected decision making and GMV in heroin abusers compared with controls. The precise neural mechanisms that underlie these associations are unknown, which requires future investigations of the effects of ZNF804A on both dopamine neurotransmission and the relative increases in the volume of various brain areas.
authors.affiliation: National Institute on Drug Dependence, Peking University, China.|Beijing Key Laboratory on Drug Dependence Research, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: National Institute on Drug Dependence, Peking University, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Zhao
authors.affiliation: Peking University, China.|Institute of Material Medical, Peking Union Medical College, Chinese Academy of Medical Sciences, China.
authors.forename: Gui-Bin
authors.initials: GB
authors.lastname: Wang
authors.affiliation: Institute of Mental Health/Peking University Sixth Hospital, Key Laboratory of Mental Health, Peking University, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Yue
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China.
authors.forename: Qi-Xiang
authors.initials: QX
authors.lastname: Lin
authors.affiliation: Department of Alcohol and Drug Dependence, Beijing Hui Long Guan Hospital, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: National Institute on Drug Dependence, Peking University, China.|Beijing Key Laboratory on Drug Dependence Research, China.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: Li
authors.affiliation: National Institute on Drug Dependence, Peking University, China.|Beijing Key Laboratory on Drug Dependence Research, China.
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.affiliation: National Institute on Drug Dependence, Peking University, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
authors.affiliation: National Institute on Drug Dependence, Peking University, China.|Beijing Key Laboratory on Drug Dependence Research, China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiology, Zhongshan Traditional Chinese Medicine Hospital, China.
authors.forename: Yu-De
authors.initials: YD
authors.lastname: Tang
authors.affiliation: Department of Radiology, Zhongshan Traditional Chinese Medicine Hospital, China.
authors.forename: Shu-Xue
authors.initials: SX
authors.lastname: Liu
authors.affiliation: Zhongshan Addiction Treatment Center, China.
authors.forename: Gui-Fa
authors.initials: GF
authors.lastname: Deng
authors.affiliation: Zhongshan Addiction Treatment Center, China.
authors.forename: Gan-Huan
authors.initials: GH
authors.lastname: Diao
authors.affiliation: Department of Alcohol and Drug Dependence, Beijing Hui Long Guan Hospital, China.
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Tan
authors.affiliation: Department of Radiology, Peking University Third Hospital, China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Han
authors.affiliation: National Institute on Drug Dependence, Peking University, China.|Institute of Mental Health/Peking University Sixth Hospital, Key Laboratory of Mental Health, Peking University, China.|Beijing Key Laboratory on Drug Dependence Research, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lin
authors.affiliation: National Institute on Drug Dependence, Peking University, China.|Beijing Key Laboratory on Drug Dependence Research, China.|The State Key Laboratory of Natural and Biomimetic Drugs, China.|Key Laboratory for Neuroscience of the Ministry of Education and the Ministry of Public Health, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
mesh_terms: D000328:Adult; D000483:Alleles; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D003071:Cognition; D003657:Decision Making; D005260:Female; D020022:Genetic Predisposition to Disease; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006239:Haplotypes; D006556:Heroin Dependence / Q000235:genetics* / Q000523:psychology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human
keywords: Decision making; ZNF804A variants; genotype; gray matter volume; haplotype; heroin addiction