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基因表达水平可量化对疾病的遗传影响
2020-05-19 13:22

美国Broad研究所Alexander Gusev和美国哈佛医学院团队合作取得新进展。他们表明可通过测定的基因表达水平量化对疾病的遗传影响。相关论文发表在2020518日的《自然—遗传学》上。

他们介绍了一种新的方法,介导的表达评分回归(MESC),以估计由基因表达水平的顺式遗传成分介导的疾病遗传力。他们将MESC应用于来自基因型组织表达(GTEx)联盟的42个性状的全基因组关联研究(GWAS)摘要统计(平均N = 323,000),和48个组织的cis-表达定量性状基因座(eQTL)摘要统计。平均每个性状,只有11±2%的遗传力由测定的基因表达水平介导。表达介导的遗传力在具有选择性约束证据的基因和具有疾病适当注释的基因中得到了富集。

他们的结果表明,虽然与疾病相关,但测定的大块组织eQTL不能解释大多数疾病的遗传力。

研究人员表示,通过GWAS鉴定出的疾病变体往往与eQTL重叠,但是尚不清楚这种重叠是否由介导疾病遗传效应的基因表达水平驱动。

附:英文原文

Title: Quantifying genetic effects on disease mediated by assayed gene expression levels

Author: Douglas W. Yao, Luke J. OConnor, Alkes L. Price, Alexander Gusev

Issue&Volume: 2020-05-18

Abstract: Disease variants identified by genome-wide association studies (GWAS) tend to overlap with expression quantitative trait loci (eQTLs), but it remains unclear whether this overlap is driven by gene expression levels ‘mediating’ genetic effects on disease. Here, we introduce a new method, mediated expression score regression (MESC), to estimate disease heritability mediated by the cis genetic component of gene expression levels. We applied MESC to GWAS summary statistics for 42 traits (average N=323,000) and cis-eQTL summary statistics for 48 tissues from the Genotype-Tissue Expression (GTEx) consortium. Averaging across traits, only 11±2% of heritability was mediated by assayed gene expression levels. Expression-mediated heritability was enriched in genes with evidence of selective constraint and genes with disease-appropriate annotations. Our results demonstrate that assayed bulk tissue eQTLs, although disease relevant, cannot explain the majority of disease heritability.

DOI: 10.1038/s41588-020-0625-2

Source: https://www.nature.com/articles/s41588-020-0625-2

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

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