Abstract 5705: Identifying DNA methylation quantitative trait loci across multi-ethnic populations

Objective: To date, genome-wide association studies (GWAS), which are primarily conducted in Europeans, have identified a large number of validated DNA methylation quantitative trait loci (meQTLs) acting in both cis and trans. However, it is recognized that there are racial differences in genetic architectures such as allele frequencies and linkage equilibrium patterns, which may differentially influence DNA methylation levels. This points to a critical need to conduct a methylome wide association study (MWAS) to identify meQTLs across multiethnic populations including understudied African Americans (AAs), Latinos, Japanese Americans (JAs), and Native Hawaiians (NHs). Methods: We are performing a GWAS to identify meQTLs in blood leukocytes in a multiethnic population using data from the Multiethnic Cohort Study (MEC). In MEC, “genome-wide” germline genetic variants and DNA methylation levels of blood leukocytes have been measured using the Illumina 1M and MethEPIC array, respectively, for 372 AAs, 408 Latinos, 531 JAs, 319 NHs, and 406 European Americans who were current smokers at time of blood draw. Genotyped data has been imputed with 1000 Genomes phase 3 dataset. For DNA methylation data, standardized quality control (QC) and normalization have been performed. We adjusted for the following potential confounders at time of blood draw: age, sex, body mass index, estimated cell type composition variables, genetic principal components, smoking pack-years, and urinary total nicotine equivalents (a biomarker for internal smoking dose). A stringent Bonferroni-corrected threshold (P