DNA methylation QTL mapping across diverse human tissues provides molecular links between genetic variation and complex traits
Year: 2022
Type: article
Abstract: Epigenetic modifications of chromosomes, including DNA methylation (DNAm), play a fundamental role in gene regulation in humans. We generated DNAm data for 987 samples from the Genotype-Tissue Expression (GTEx) project, representing 9 tissue types and 424 subjects. We integrated GTEx RNA-seq data to examine methylome-transcriptome associations, their tissue specificity, and their overlap with regulatory regions. We mapped DNAm quantitative trait loci in cis (mQTLs), contrasted mQTLs with expression QTLs (eQTLs) with respect to functional elements, and assessed their relative contributions to complex traits. We identified thousands of mQTL links to traits in locations lacking a relevant eQTL. By integrating genetic, diverse -omics and phenotype data, we contribute to the understanding of molecular regulatory mechanisms in human tissues and their association with complex traits.
Source: Nature Genetics
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Health and Human Services, University of Chicago, Broad Institute, Centre de Regulació Genòmica, Health Services Research Programme, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences
Awards: G2421595363, Medical Scientist National Research Service Award, Integrative multivariate association and genomic analyses, Arsenic and the Human Genome: susceptibility and response to exposure, Systems Biology based Proteogenomic Translator for Cancer Marker Discovery towards Precision Medicine, Telomere length and chromosomal instability across various tissue types, G4973783208, G5287529264, Genetic mechanisms underlying sexual dimorphism in cancer and response to therapy, G6503177986, ChicAgo Center for Health and EnvironmenT (CACHET)
OpenAlex ID: W4312064742