Sex chromosome-wide association analysis suggested male-specific risk genes for alcohol dependence
Sex chromosome-wide association analysis suggested male-specific risk genes for alcohol dependence
复制标题
DOI：
10.1097/ypg.0b013e328364b8c7
复制
发表时间：
2013-12-01
影响因子：
0.9
通讯作者：
Luo, Xingguang
中科院分区：
文献类型：
--
作者：
Zuo, Lingjun;Wang, Kesheng;Luo, Xingguang
背景酒精依赖在男性中比在女性中更常见。对此的潜在解释包括性染色体（X和Y）中基因的作用。在本研究中，我们扫描了整个Y染色体和它的同源物的X染色体的男性，以确定男性特定的风险基因酒精dependance.MethodsTwo千九百二十七个人在两个独立的队列进行了分析。欧美男性队列（883例酒精依赖和445例对照）作为发现队列，欧美女性队列（526例和1073例对照）作为对照组。在Illumina Human 1 M微珠芯片上对所有个体进行基因分型。分析了Y染色体或X染色体同源物上的2224个单核苷酸多态性（SNP）。使用logistic回归分析比较每个队列中病例和对照之间的等位基因频率。ResultsWe发现，在实验范围内校正后，X染色体上的两个SNP与欧美男性的酒精依赖显著相关（在NLGN 4X的3个UTR处，rs 5916144的P=1.0x10（-4），rs 5961794的P=5.5x10（-5）），但在女性中没有。在NLGN 4X的3UTR处或NLGN 4X内的总共26个SNPs名义上与男性酒精依赖相关（5.5x10（-5 P0. 05），所有这些在女性中均不具有统计学显著性。NLGN 4X可能具有酒精依赖的因果变异。由NLGN 4X突变引起的神经元回路中的突触发生缺陷被认为在酒精依赖中起作用。
BackgroundAlcohol dependence is more common among men than among women. Potential explanations for this include the role of genes in sex chromosomes (X and Y). In the present study, we scanned the entire Y chromosome and its homologs on the X chromosome in men to identify male-specific risk genes for alcohol dependence.MethodsTwo thousand nine hundred and twenty-seven individuals in two independent cohorts were analyzed. The European-American male cohort (883 cases with alcohol dependence and 445 controls) served as the discovery cohort and the European-American female cohort (526 cases and 1073 controls) served as a contrast group. All individuals were genotyped on the Illumina Human 1M beadchip. Two thousand two hundred and twenty-four single nucleotide polymorphisms (SNPs) on the Y chromosome or in the homologs on the X chromosome were analyzed. The allele frequencies were compared between cases and controls within each cohort using logistic regression analysis.ResultsWe found that, after experiment-wide correction, two SNPs on the X chromosome were associated significantly with alcohol dependence in European-American men (P=1.0x10(-4) for rs5916144 and P=5.5x10(-5) for rs5961794 at 3 UTR of NLGN4X), but not in the women. A total of 26 SNPs at 3UTR of or within NLGN4X were nominally associated with alcohol dependence in men (5.5x10(-5)P0.05), all of which were not statistically significant in women.ConclusionWe conclude that NLGN4X was a significant male-specific risk gene for alcohol dependence in European-Americans. NLGN4X might harbor a causal variant(s) for alcohol dependence. A defect of synaptogenesis in neuronal circuitry caused by NLGN4X mutations is believed to play a role in alcohol dependence.