Human populations have substantial genetic diversity,but the extent of epigenetic diversity remains unclear,as population-specific DNA methylation(DNAm)has only been studied for�3.0%of CpGs.In this study,we quantified...Human populations have substantial genetic diversity,but the extent of epigenetic diversity remains unclear,as population-specific DNA methylation(DNAm)has only been studied for�3.0%of CpGs.In this study,we quantified DNAm using whole-genome bisulfite sequencing(WGBS)and analyzed it alongside whole-genome genotype data to provide a more comprehensive view of population-specific DNAm.Using a co-methylated region(CMR)approach,36,657 CMRs were identified in WGBS data from 62 lymphoblastoid B-cell line(LCL)samples,with subsequent validation in a combined array dataset of 326 LCL samples.Between individuals of European and African ancestry,101 CMRs exhibited population-specific DNAm patterns(Pop-CMRs),including 91 Pop-CMRs not reported in previous investigations.These regions spanned genes(e.g.,CCDC42,GYPE,MAP3K20,and OBI1)related to diseases(e.g.,malaria infection and diabetes)with differing prevalence and incidence between populations.Over half of the Pop-CMRs were associated with genetic variants,displaying population-specific allele frequencies and primarily mapped to genes involved in metabolic and infectious processes.Additionally,subsets of Pop-CMRs were applicable in East Asian populations and peripheral blood-based tissues.This study highlights genome-wide DNAm differences between populations and examines their associations with genetic varation and biological relevance,advancing our understanding of epigenetic contributions to population specificity.展开更多
基金funded by the Genome ScienceþTechnology Programsupported by the Genome ScienceþTechnology Program and an NSERC CREATE bursary via the UBC ECOSCOPE Program+3 种基金supported by a Fredrick Banting and Charles Best Canada Graduate Scholarships(CGS-D)award from the Canadian Institutes of Health Researchfunded by the Sunny Hill Health Centre BC Leadership Chair in Early Childhood Development Endowment Trust Fundfunding from the BC Children’s Hospital Research Institute’s Establishment Award and Investigator Grant Award Programthe Natural Sciences and Engineering Research Council of Canada.
文摘Human populations have substantial genetic diversity,but the extent of epigenetic diversity remains unclear,as population-specific DNA methylation(DNAm)has only been studied for�3.0%of CpGs.In this study,we quantified DNAm using whole-genome bisulfite sequencing(WGBS)and analyzed it alongside whole-genome genotype data to provide a more comprehensive view of population-specific DNAm.Using a co-methylated region(CMR)approach,36,657 CMRs were identified in WGBS data from 62 lymphoblastoid B-cell line(LCL)samples,with subsequent validation in a combined array dataset of 326 LCL samples.Between individuals of European and African ancestry,101 CMRs exhibited population-specific DNAm patterns(Pop-CMRs),including 91 Pop-CMRs not reported in previous investigations.These regions spanned genes(e.g.,CCDC42,GYPE,MAP3K20,and OBI1)related to diseases(e.g.,malaria infection and diabetes)with differing prevalence and incidence between populations.Over half of the Pop-CMRs were associated with genetic variants,displaying population-specific allele frequencies and primarily mapped to genes involved in metabolic and infectious processes.Additionally,subsets of Pop-CMRs were applicable in East Asian populations and peripheral blood-based tissues.This study highlights genome-wide DNAm differences between populations and examines their associations with genetic varation and biological relevance,advancing our understanding of epigenetic contributions to population specificity.
