The EWAS Catalog: a database of epigenome-wide association studies

Abstract

Epigenome-wide association studies (EWAS) seek to quantify associations between traits/exposures and DNA methylation measured at thousands or millions of CpG sites across the genome. In recent years, the increase in availability of DNA methylation measures in population-based cohorts and case-control studies has resulted in a dramatic expansion of the number of EWAS being performed and pub-lished. To make this rich source of results more accessible, we have manually curated a database of CpG-trait associations (with p<1x10-4) from published EWAS, each assaying over 100,000 CpGs in at least 100 individuals. From 2021-01-29, The EWAS Catalog contained 1,045,303 associations from over 1000 EWAS. This includes 652,530 associations from 264 peer-reviewed publications. In addi-tion, it also contains summary statistics for 392,773 associations from 428 EWAS, performed in data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Gene Expression Om-nibus (GEO). The database is accompanied by a web-based tool and R package, giving researchers the opportunity to quickly and easily query EWAS associations and gain insight into the molecular under-pinnings of disease as well as the impact of traits and exposures on the DNA methylome. The EWAS Catalog is available at: http://www.ewascatalog.org.

Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer’s disease

“…Using a PubMed search (using "{gene name} AND alzheimer*} as search terms) revealed that no publication exists to date directly linking any of these genes to AD. Look-up of the CpG IDs on the EWAS Catalog (http://www.ewascatalog.org/) 37 revealed that cg03073402 and cg20648333 were previously reported to be associated with aging from birth to late adolescence in blood samples 38 .…”

Genome-wide methylation data improves dissection of the effect of smoking on body mass index

“…These smoking associated CpG sites could also be picking up variation from other environmental sources that are not exclusively driven by smoking, but correlated with it, such as alcohol intake. When checking in the literature for other possible associations between the 62 CpG sites and other environmental measures ( S9 Table ), 20 of these CpGs have previously been associated with age, 15 with alcohol intake or alcohol dependence, 11 with educational attainment, 10 with different types of cancer; and a few with other diseases [ 45 , 46 ]. Unlike for smoking, for most of these associations with other traits, it is unclear if they are casual, or if they could as well be driven by smoking (e.g., alcohol consumption is associated with smoking and picking up a smoking signal).…”

Genome-wide DNA methylation analysis on C-reactive protein among Ghanaians suggests molecular links to the emerging risk of cardiovascular diseases

“…In post-hoc evaluations, we found that DMPs in PC, BTG4 and PADI1 showed trends of associations with estimated CVD risk, we identified a separate DMP in MORC2 that was associated with CRP levels ≤10 mg/L, and we successfully replicated 65 (24%) of previously reported CRP associated DMPs. All DMPs with gene annotations (13) were biologically linked to inflammation or CVD traits.…”

“…We, therefore, performed an epigenome-wide association study (EWAS) to identify differentially methylated loci associated with CRP among Ghanaians. Subsequently, we assessed whether these detected loci were associated with the 10year estimated risk of CVD in the same population, or with CVD in previous genome/epigenome-wide association studies 13,14 .…”