通路分析提示钙信号转导通路与酒精依赖关联

Pathway Analysis Suggest the Calcium Signaling Pathway Associated with Alcohol Dependence

摘要: 背景：酒精依赖是一种严重而常见的复杂疾病，大量关联研究常致力寻找其易感基因，目前对已发现的遗传变异还缺乏整体的分析和认识。方法：采用基因富集通路分析法对来自31项饮酒相关研究的1438个单核苷酸多态性进行分析。结果：钙信号传导通路(hsa04020) (P = 5.4 ´ 10−5)显示出最显著的关联富集，经多重检验校正后仍显著(bonferroni P = 0.8 ´ 10−3, FDR = 0.6 ´ 10−2)。有研究证实钙信号转导通路在脑功能调节中必不可少，该通路中的基因与酒精对身体的抑郁作用有关。结论：钙信号转导通路可能对酒精依赖具有重要影响。

Abstract: Background: Alcohol dependence (AD) is a serious and common public health problem. A large number of association studies were conducted to identify susceptibility genes of AD, but efforts to generate an integrate view of accumulative genetic variants and pathways under alcohol drinking are lacking. Methods: We applied enrichment gene set analysis to existing genetic association results to identify pertinent pathways to alcohol dependence in this study. A total of 1438 SNPs (P < 1.0 ´ 10−3) associated to alcohol drinking related-traits have been collected from 31 studies. Results: The calcium signaling pathway (hsa04020) showed the most significant enrichment of associations (21 genes) to alcohol consumption phenotypes (P = 5.4 ´ 10−5), achieving bonferroni P value of 0.8 ´ 10−3 and FDR value of 0.6 ´ 10−2, respectively. Interestingly, the calcium signaling pathway was previously found to be essential to regulate brain function. Genes in this pathway link to a depressive effect of alcohol consumption on the body. Conclusions: Our findings, together with previous biological evidence suggest the importance of gene polymorphisms of calcium signaling pathway to alcohol dependence susceptibility.