Identification of rare disease genes as drivers of common diseases through tissue-specific gene regulatory networks.

ABSTRACT: Genetic variants identified through genome-wide association studies (GWAS) are typically non-coding, exerting small regulatory effects on downstream genes. However, which downstream genes are ultimately impacted and how they confer risk remains mostly unclear. By contrast, variants that cause rare Mendelian diseases are often coding and have a more direct impact on disease development. Here we demonstrate that common and rare genetic diseases can be linked by studying how common disease-associated variants influence gene co-expression in 57 different tissues and cell types. We implemented this method in a framework called Downstreamer and applied it to 88 GWAS traits. We find that predicted downstream "genes" are enriched with Mendelian disease genes, e.g. key genes for height are enriched

SUBMITTER: Bakker OB 

PROVIDER: S-EPMC11618476 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature