Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Database (Oxford). 2018 Jan 1;2018:bay121. doi: 10.1093/database/bay121.
Studies have shown that genetic factors play an important role in the risk to substance addiction and abuse. So far, various genetic and genomic studies have reported the related evidence. These rich, but highly heterogeneous, data provide us an unprecedented opportunity to systematically collect, curate and assess the genetic and genomic signals from published studies and to perform a comprehensive analysis of their features, functional roles and druggability. Such genetic data resources have been made available for other disease or phenotypes but not for major substance dependence yet. Here, we report comprehensive data collection and secondary analyses of four phenotypes of dependence: alcohol dependence, nicotine dependence, cocaine dependence and opioid dependence, collectively named as Alcohol, Nicotine, Cocaine and Opioid (ANCO) dependence. We built the ANCO-GeneDB, an ANCO-dependence-associated gene resource database. ANCO-GeneDB includes resources from genome-wide association studies and candidate gene-based studies, transcriptomic studies, methylation studies, literature mining and drug-target data, as well as the derived data such as spatial-temporal gene expression, promoters, enhancers and expression quantitative trait loci. All associated genes and genetic variants are well annotated by using the collected evidence. Based on the collected data, we performed integrative, secondary analyses to prioritize genes, pathways, eQTLs and tissues that are significantly enriched in ANCO-related phenotypes.
研究表明，遗传因素在物质成瘾和滥用的风险中起着重要作用。到目前为止，各种遗传和基因组研究已经报告了相关证据。这些丰富但高度异质的数据为我们提供了一个前所未有的机会，可以系统地收集、整理和评估已发表研究中的遗传和基因组信号，并对其特征、功能作用和可用药性进行全面分析。这些遗传数据资源已经可用于其他疾病或表型，但尚未用于主要物质依赖。在这里，我们报告了对四种依赖表型（酒精依赖、尼古丁依赖、可卡因依赖和阿片依赖）的综合数据收集和二次分析，统称为酒精、尼古丁、可卡因和阿片（ANCO）依赖。我们构建了 ANCO-GeneDB，这是一个与 ANCO 依赖相关的基因资源数据库。ANCO-GeneDB 包括来自全基因组关联研究和候选基因研究、转录组研究、甲基化研究、文献挖掘和药物靶点数据的资源，以及时空基因表达、启动子、增强子和表达数量性状位点等衍生数据。所有相关基因和遗传变异都使用收集到的证据进行了很好的注释。基于收集到的数据，我们进行了综合的二次分析，以确定在 ANCO 相关表型中显著富集的基因、途径、eQTLs 和组织。
