B4035 - Genetic basis of DNA methylation - 13/04/2022

B number: 
Principal applicant name: 
Josine Min | MRC IEU, University of Bristol (United Kingdom)
Caroline Relton, Gibran Hemani, Tom Gaunt
Title of project: 
Genetic basis of DNA methylation
Proposal summary: 

DNA methylation (DNAm) plays a central role in gene regulation. It helps to define how cells respond to environmental signals and, ultimately, contributes to health or susceptibility to disease. DNAm variation is influenced by genetic, molecular and environmental and other factors. However, the amount and the effects of differences in DNAm from one person to another is poorly understood.

A powerful avenue into researching the functional consequences of changes in DNAm levels is to correlate DNA sequence variants such as single nucleotide polymorphism (SNPs) to DNAm levels to find both local and distal (for example on other chromosomes) effects. Having completed the largest genetic study of DNAm worldwide to date (through the Genetics of DNA Methylation Consortium) by scanning 10 million SNPs genomewide, we have identified 270k SNP-DNAm associations. This was achieved by analysing about 400,000 DNAm sites in blood, which is only 2% of 28 million DNAm sites across the genome. There is a huge potential for improved understanding of DNAm variation between individuals and its influence on health and disease by studying other regulatory regions of the genome using EPIC arrays and by comparing different ethnicities. We propose to systematically map genetic influences on DNAm and to compare these genetic influences across ancestries.

Impact of research: 
Date proposal received: 
Tuesday, 5 April, 2022
Date proposal approved: 
Wednesday, 13 April, 2022
Genetic epidemiology (including association studies and mendelian randomisation), Statistical methods, Genetic epidemiology