Liu Lei, Zhang Bo, Dong Yong, Liu Li Ping, Wang Jing Ying, Liu Jun, Zhou Guang Yu, Kang Chuan Yi, Hu Xiaorui, Cheng Chang, Zhao Na, Lu Jia, Wang Huaizhi, Hu Jian, Wang Xiaohong
Department of Psychiatry, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of Psychology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Addict Biol. 2025 Aug;30(8):e70070. doi: 10.1111/adb.70070.
Alcohol use disorder is closely related to genetic and environmental factors. However, the contribution of coding variation to alcohol use disorder susceptibility remains poorly understood. We aimed to identify genetic mutations in alcohol use disorder by whole exon sequencing. We performed whole-exome sequencing in 83 patients with alcohol use disorder and compared it with exome sequences of healthy controls that were collected from the 1000 Genomes Project. GO and KEGG enrichment analysis and protein interaction analysis were performed for the mutated genes in each group. Three online protein function prediction sites were used to predict whether SNPs/InDels cause protein coding changes. Further, we conducted a rare variant exploration. We identified 106 525 SNV and 19 826 InDel gene mutations in alcohol use disorder. In the healthy and alcohol use disorder groups, mutations in CNTNAP3, ZNF683, ALDPH2, CCHCR1, ZNF45 and ESRRA loci were found to be deleterious mutations in all three sites; CNTNAP3, ZNF683, ALDPH2, CCHCR1, ZNF45 and ESRRA may be potential targets for future precision treatment of alcohol use disorders, and further provide new ideas for drug development.
酒精使用障碍与遗传和环境因素密切相关。然而，编码变异对酒精使用障碍易感性的贡献仍知之甚少。我们旨在通过全外显子测序确定酒精使用障碍中的基因突变。我们对83例酒精使用障碍患者进行了全外显子测序，并将其与从千人基因组计划收集的健康对照的外显子序列进行比较。对每组中的突变基因进行了GO和KEGG富集分析以及蛋白质相互作用分析。使用三个在线蛋白质功能预测位点来预测单核苷酸多态性/插入缺失是否会导致蛋白质编码变化。此外，我们进行了罕见变异探索。我们在酒精使用障碍中鉴定出106525个单核苷酸变异和19826个插入缺失基因突变。在健康组和酒精使用障碍组中，发现接触蛋白相关蛋白3（CNTNAP3）、锌指蛋白683（ZNF683）、醛脱氢酶2（ALDPH2）、富含半胱氨酸的卷曲螺旋蛋白1（CCHCR1）、锌指蛋白45（ZNF45）和雌激素相关受体α（ESRRA）基因座的突变在所有三个位点都是有害突变；CNTNAP3、ZNF683、ALDPH2、CCHCR1、ZNF45和ESRRA可能是未来酒精使用障碍精准治疗的潜在靶点，并进一步为药物开发提供新思路。
