ZNF804A variants confer risk for heroin addiction and affect decision making and gray matter volume in heroin abusers.
- Authors
- Sun, Yan; Zhao, Li-Yan; Wang, Gui-Bin; Yue, Wei-Hua; He, Yong; Shu, Ni; Lin, Qi-Xiang; Wang, Fan; Li, Jia-Li; Chen, Na; Wang, Hui-Min; Kosten, Thomas R; Feng, Jia-Jia; Wang, Jun; Tang, Yu-De; Liu, Shu-Xue; Deng, Gui-Fa; Diao, Gan-Huan; Tan, Yun-Long; Han, Hong-Bin; Lin, Lu; Shi, Jie
- Year
- 2016
- Journal
- Addiction biology
- PMID
- 25708696
- DOI
- 10.1111/adb.12233
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.
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Human Genetics of Addiction: New Insights and Future Directions. | 2018 | 29504045 |
| Replication of ZNF804A gene variant associations with risk of heroin addiction. | 2015 | 26382569 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| ANK3 rs10994336 and ZNF804A rs7597593 polymorphisms: genetic interaction for emotional and behavioral symptoms of alcohol withdrawal syndrome. | Shen G et al. | — | 2024 | → |
| Impulsivity and aggression in alcohol withdrawal syndrome is modulated by the interaction of ZNF804A and mTOR polymorphism. | Shen G et al. | — | 2024 | → |
| Long-access heroin self-administration induces region specific reduction of grey matter volume and microglia reactivity in the rat. | Cannella N et al. | — | 2024 | → |
| Transcriptomic effects of paternal cocaine-seeking on the reward circuitry of male offspring. | Huang N et al. | — | 2024 | → |
| Effects of fentanyl self-administration on risk-taking behavior in male rats. | Wheeler AR et al. | — | 2023 | → |
| Genome-wide by environment interaction studies of maternal smoking and educational score in UK biobank. | Huang H et al. | — | 2023 | → |
| Identification of a sex-stratified genetic algorithm for opioid addiction risk. | Bright D et al. | — | 2021 | → |
| The Interaction Between Genetic Variant ZNF804A rs1344706 and Alcohol Withdrawal on Impulsivity: Evidence for the Diathesis-Stress Model. | Zhang X et al. | — | 2021 | → |
| Genome-Wide Meta-Analyses of FTND and TTFC Phenotypes. | Chen J et al. | — | 2020 | → |
| Gray matter alteration in heroin-dependent men: An atlas-based magnetic resonance imaging study. | Shi H et al. | — | 2020 | → |
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| Replication of ZNF804A gene variant associations with risk of heroin addiction. | Hancock DB et al. | — | 2015 | → |