UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Genetic impacts on DNA methylation help elucidate regulatory genomic processes

Villicaña, Sergio; Castillo-Fernandez, Juan; Hannon, Eilis; Christiansen, Colette; Tsai, Pei-Chien; Maddock, Jane; Kuh, Diana; ... Bell, Jordana T; + view all (2023) Genetic impacts on DNA methylation help elucidate regulatory genomic processes. Genome Biology , 24 (1) , Article 176. 10.1186/s13059-023-03011-x. Green open access

[thumbnail of s13059-023-03011-x.pdf]
Preview
PDF
s13059-023-03011-x.pdf - Published Version

Download (2MB) | Preview

Abstract

BACKGROUND: Pinpointing genetic impacts on DNA methylation can improve our understanding of pathways that underlie gene regulation and disease risk. RESULTS: We report heritability and methylation quantitative trait locus (meQTL) analysis at 724,499 CpGs profiled with the Illumina Infinium MethylationEPIC array in 2358 blood samples from three UK cohorts. Methylation levels at 34.2% of CpGs are affected by SNPs, and 98% of effects are cis-acting or within 1 Mbp of the tested CpG. Our results are consistent with meQTL analyses based on the former Illumina Infinium HumanMethylation450 array. Both SNPs and CpGs with meQTLs are overrepresented in enhancers, which have improved coverage on this platform compared to previous approaches. Co-localisation analyses across genetic effects on DNA methylation and 56 human traits identify 1520 co-localisations across 1325 unique CpGs and 34 phenotypes, including in disease-relevant genes, such as USP1 and DOCK7 (total cholesterol levels), and ICOSLG (inflammatory bowel disease). Enrichment analysis of meQTLs and integration with expression QTLs give insights into mechanisms underlying cis-meQTLs (e.g. through disruption of transcription factor binding sites for CTCF and SMC3) and trans-meQTLs (e.g. through regulating the expression of ACD and SENP7 which can modulate DNA methylation at distal sites). CONCLUSIONS: Our findings improve the characterisation of the mechanisms underlying DNA methylation variability and are informative for prioritisation of GWAS variants for functional follow-ups. The MeQTL EPIC Database and viewer are available online at https://epicmeqtl.kcl.ac.uk .

Type: Article
Title: Genetic impacts on DNA methylation help elucidate regulatory genomic processes
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13059-023-03011-x
Publisher version: https://doi.org/10.1186/s13059-023-03011-x
Language: English
Additional information: © 2023 BioMed Central Ltd. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: DNA methylation, Heritability, GWAS, Methylation quantitative trait loci, meQTL
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Epidemiology and Applied Clinical Research
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
URI: https://discovery.ucl.ac.uk/id/eprint/10174800
Downloads since deposit
14Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item