美国芝加哥大学Brandon L. Pierce，Lin S. Chen和Meritxell Oliva共同合作，近期取得重要工作进展。他们研究发现不同人类组织DNA甲基化QTL图谱可提供遗传变异和复杂性状之间的分子联系。相关研究成果2022年12月12日在线发表于《自然—遗传学》杂志上。
据介绍，人固体组织中DNA甲基化（DNAm）的研究相对较少，为了解DNAm在基因调控中的作用及其与复杂性状的相关性，需要对其进行组织特异性的描述。
研究人员为来自基因型组织表达（GTEx）项目的987个人类样本生成基于阵列的DNAm图谱，代表9种组织类型和424名受试者。他们对甲基组和转录组相关性（eQTMs）、跨组织的顺式遗传调控（mQTL和eQTL）以及e/mQTL与复杂性状的联系进行了表征。研究人员鉴定出286152个CpG位点的mQTL，其中许多（>5%）表现出组织特异性，并且mQTL共定位了83个性状中2254个不同的GWAS位点。对于91%的这些基因座，通过整合功能图（包括eQTM和/或eQTL共定位）确定了候选基因链接，但只有33%的基因座涉及同一组织类型中存在的eQTL和mQTL。
总之，通过这种以DNA为中心的综合分析，有助于人们理解人类组织中的分子调控机制及其对复杂性状的影响。
附：英文原文
Title: DNA methylation QTL mapping across diverse human tissues provides molecular links between genetic variation and complex traits
Author: Oliva, Meritxell, Demanelis, Kathryn, Lu, Yihao, Chernoff, Meytal, Jasmine, Farzana, Ahsan, Habibul, Kibriya, Muhammad G., Chen, Lin S., Pierce, Brandon L.
Issue&Volume: 2022-12-12
Abstract: Studies of DNA methylation (DNAm) in solid human tissues are relatively scarce; tissue-specific characterization of DNAm is needed to understand its role in gene regulation and its relevance to complex traits. We generated array-based DNAm profiles for 987 human samples from the Genotype-Tissue Expression (GTEx) project, representing 9 tissue types and 424 subjects. We characterized methylome and transcriptome correlations (eQTMs), genetic regulation in cis (mQTLs and eQTLs) across tissues and e/mQTLs links to complex traits. We identified mQTLs for 286,152 CpG sites, many of which (>5%) show tissue specificity, and mQTL colocalizations with 2,254 distinct GWAS hits across 83 traits. For 91% of these loci, a candidate gene link was identified by integration of functional maps, including eQTMs, and/or eQTL colocalization, but only 33% of loci involved an eQTL and mQTL present in the same tissue type. With this DNAm-focused integrative analysis, we contribute to the understanding of molecular regulatory mechanisms in human tissues and their impact on complex traits.
DOI: 10.1038/s41588-022-01248-z
Source: https://www.nature.com/articles/s41588-022-01248-z
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
