{"doi":"10.1038/s42003-022-03353-5","title":"Incorporating local ancestry improves identification of ancestry-associated methylation signatures and meQTLs in African Americans","abstract":"<jats:title>Abstract</jats:title><jats:p>Here we report three epigenome-wide association studies (EWAS) of DNA methylation on self-reported race, global genetic ancestry, and local genetic ancestry in admixed Americans from three sets of samples, including internal and external replications (<jats:italic>N</jats:italic><jats:sub>total </jats:sub>= 1224). Our EWAS on local ancestry (LA) identified the largest number of ancestry-associated DNA methylation sites and also featured the highest replication rate. Furthermore, by incorporating ancestry origins of genetic variations, we identified 36 methylation quantitative trait loci (meQTL) clumps for LA-associated CpGs that cannot be captured by a model that assumes identical genetic effects across ancestry origins. Lead SNPs at 152 meQTL clumps had significantly different genetic effects in the context of an African or European ancestry background. Local ancestry information enables superior capture of ancestry-associated methylation signatures and identification of ancestry-specific genetic effects on DNA methylation. These findings highlight the importance of incorporating local ancestry for EWAS in admixed samples from multi-ancestry cohorts.</jats:p>","journal":"Communications Biology","year":2022,"id":45054,"datarank":0.6102302906169461,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.1608704495838474,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.1608704495838474,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":11,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":4,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":211062,"name":"Bradley E. Aouizerat","orcid":null,"position":1,"is_corresponding":false},{"id":211066,"name":"Youshu Cheng","orcid":null,"position":2,"is_corresponding":false},{"id":211067,"name":"Kathryn Anastos","orcid":"0000-0002-0769-6405","position":3,"is_corresponding":false},{"id":207366,"name":"Amy C. Justice","orcid":"0000-0003-0139-5502","position":4,"is_corresponding":false},{"id":2737,"name":"Luca Pinello","orcid":"0000-0003-1195-9607","position":5,"is_corresponding":false},{"id":55236,"name":"Ke Xu","orcid":"0000-0002-8130-1109","position":6,"is_corresponding":false},{"id":211060,"name":"Boyang Li","orcid":"0000-0003-2808-9986","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":4,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35488087","pmcid":"PMC9054854","openalex_id":"https://openalex.org/W4225145267","authors":[],"funders":[{"funder_name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","grant_id":"R01 DA038632","title":null},{"funder_name":"U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse","grant_id":"R01 DA047820","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146193","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146204","title":null},{"funder_name":"NIAAA NIH HHS","grant_id":"U10 AA013566","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"R03 DA039745","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146203","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P30 AI027767","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P30 AI050409","title":null},{"funder_name":"NIAAA NIH HHS","grant_id":"U01 AA020790","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146202","title":null},{"funder_name":"NIAAA NIH HHS","grant_id":"U01 AA020799","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146241","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146242","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146194","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P30 AI050410","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"R01 DA042691","title":null},{"funder_name":"NIAAA NIH HHS","grant_id":"U01 AA020795","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146245","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"R01 DA035616","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"R01 DA047063","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146192","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL146205","title":null},{"funder_name":"NIAAA NIH HHS","grant_id":"U24 AA020794","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR000004","title":null},{"funder_name":"National Institutes of Health","grant_id":"3U01HL146202-02S1","title":"MACS/WIHS Combined Cohort Study: Brooklyn Clinical Research Site (Bklyn CRS)"},{"funder_name":"National Institutes of Health","grant_id":"5R01DA047063-04","title":"Defining the impact of injection drug use on antiretroviral therapy and HIV treatment 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Veterans"},{"funder_name":"National Institutes of Health","grant_id":"5U01HL146242-07","title":"SF Bay Area MACS/WIHS Combined Cohort Study"},{"funder_name":"National Institutes of Health","grant_id":"5P30AI050410-05","title":"UNC Center for Aids Research"},{"funder_name":"U.S. Department of Health &amp; Human Services | NIH | National Institute on Drug 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