Genome-Wide Association Discoveries of Alcohol Dependence

被引：33
作者：
Zuo, Lingjun [1 ]
Lu, Lingeng [2 ]
Tan, Yunlong [3 ]
Pan, Xinghua [4 ]
Cai, Yiqiang [5 ]
Wang, Xiaoping [6 ]
Hong, Jiang [7 ]
Zhong, Chunlong [8 ]
Wang, Fei [1 ]
Zhang, Xiang-Yang [9 ]
Vanderlinden, Lauren A. [10 ]
Tabakoff, Boris [10 ]
Luo, Xingguang [1 ,3 ]
机构：
[1] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA
[2] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA
[3] Beijing Huilongguan Hosp, Biol Psychiat Res Ctr, Beijing, Peoples R China
[4] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA
[5] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA
[6] Shanghai Jiao Tong Univ, Peoples Hosp 1, Dept Neurol, Shanghai 200030, Peoples R China
[7] Shanghai Jiao Tong Univ, Peoples Hosp 1, Dept Emergency, Shanghai 200030, Peoples R China
[8] Shanghai Jiao Tong Univ, Renji Hosp, Dept Neurosurg, Shanghai 200030, Peoples R China
[9] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA
[10] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA
来源：
AMERICAN JOURNAL ON ADDICTIONS | 2014年 / 23卷 / 06期
关键词：
LONG NONCODING RNAS; QUANTITATIVE-TRAIT; NUCLEUS-ACCUMBENS; CLASS-III; GENE; RISK; IDENTIFICATION; EXPRESSION; SEROTONIN; SUSCEPTIBILITY;
D O I：
10.1111/j.1521-0391.2014.12147.x
中图分类号：
R194 [卫生标准、卫生检查、医药管理];
学科分类号：
摘要：
Objective: To report the genome-wide significant and/or replicable risk variants for alcohol dependence and explore their potential biological functions. Methods: We searched in PubMed for all genome-wide association studies (GWASs) of alcohol dependence. The following three types of results were extracted: genome-wide significant associations in an individual sample, the combined samples, or the meta-analysis (p < 5 x 10(-8)); top-ranked associations in an individual sample (p < 10(-5)) that were nominally replicated in other samples (p <. 05); and nominally replicable associations across at least three independent GWAS samples (p <. 05). These results were meta-analyzed. cise-QTLs in human, RNA expression in rat and mouse brains and bioinformatics properties of all of these risk variants were analyzed. Results: The variants located within the alcohol dehydrogenase (ADH) cluster were significantly associated with alcohol dependence at the genome-wide level (p < 5 x 10(-8)) in at least one sample. Some associations with the ADH cluster were replicable across six independent GWAS samples. The variants located within or near SERINC2, KIAA0040, MREG-PECR or PKNOX2 were significantly associated with alcohol dependence at the genome-wide level (p < 5 x 10(-8)) in meta-analysis or combined samples, and these associations were replicable across at least one sample. The associations with the variants within NRD1, GPD1L-CMTM8 or MAP3K9-PCNX were suggestive (5 x 10(-8) < p < 10(-5)) in some samples, and nominally replicable in other samples. The associations with the variants at HTR7 and OPA3 were nominally replicable across at least three independent GWAS samples (10(-5) < p < .05). Some risk variants at the ADH cluster, SERINC2, KIAA0040, NRD1, and HTR7 had potential biological functions. Conclusion: The most robust risk locus was the ADH cluster. SERINC2, KIAA0040, NRD1, and HTR7 were also likely to play important roles in alcohol dependence. PKNOX2, MREG, PECR, GPD1L, CMTM8, MAP3K9, PCNX, and OPA3 might play less important roles in risk for alcohol dependence based on the function analysis. This conclusion will significantly contribute to the post-GWAS follow-up studies on alcohol dependence.
引用
收藏
页码：526 / 539
页数：14
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