A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids
Description
We examined the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identified 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observed a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a low overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.
Notes
Two sets of results files are included.
Set 1. Txt files provide the results of the epigenomide association study for each of 3 lipid traits, 3 racial/ethnic subgroups followed by a trans-ethnic meta-analysis, and 4 models. Files are labelled as lipid.model.racial/ethnic_group.GC. The three lipid trais are HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triglycerides. The three racial/ethnic groups are EA: European ancestry; AA: African ancestry; HA: Hispanic ancestry; ALL_wGOLDN: trans-ethnic. The suffix "GC" indicates that a genomic-control correction has been applied. Each file includes results for fixed effect meta-analysis as well as random effect meta-analysis where more than 1 cohort is available for analysis (p-value, beta, standard error). Each file also includes heterogeneity statitics where more than 1 cohort is meta-analyzed. Lastly, P values for each study included in the meta-analysis are provided. Please note these P values are followed by M values labelled as NA.
Set 2. CSV files provide the results of the methylation QTL association meta-analyses for 30 CpGs found to be associated with one of three lipid traits in more than one racial/ethnic group. SNPs tested are those within 25kb upstream or downstream of each CpG. Both fixed efffect and random effect meta-analysis results are provided as well as heterogeneity results when more than 1 study contributes to the meta-analysis. Each file is labelled by CpG followed by the racial/ethnic group analysed: EA: European ancestry; AA: African ancestry; HA: Hispanic ancestry.
Funding provided by: National Heart, Lung, and Blood Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000050
Award Number: HHSN268201300006C
Funding provided by: National Heart, Lung, and Blood Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000050
Award Number: R01HL105756
Funding provided by: National Heart, Lung, and Blood Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000050
Award Number: R01HL104135
Funding provided by: National Institute for Environmental Studies
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100005769
Award Number: R01ES020836
Files
cg00574958_AA.csv
Files
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