{"doi":"10.17615/tf1e-dg63","title":"Genome-wide Association Study of Susceptibility to Particulate Matter–Associated QT Prolongation","abstract":"BACKGROUND: Ambient particulate matter (PM) air pollution exposure has been associated with increases in QT interval duration (QT). However, innate susceptibility to PM-associated QT prolongation has not been characterized. OBJECTIVE: To characterize genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide association study (GWAS). METHODS: Using repeated electrocardiograms (1986–2004), longitudinal data on PM<10 μm in diameter (PM10), and generalized estimating equations methods adapted for low-prevalence exposure, we estimated approximately 2.5×106 SNP×PM10 interactions among nine Women’s Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (n=22,158), then combined subpopulation-specific results in a fixed-effects, inverse variance-weighted meta-analysis. RESULTS: A common variant (rs1619661; coded allele: T) significantly modified the QT-PM10 association (p=2.11×10−8). At PM10 concentrations >90th percentile, QT increased 7 ms across the CC and TT genotypes: 397 (95% confidence interval: 396, 399) to 404 (403, 404) ms. However, QT changed minimally across rs1619661 genotypes at lower PM10 concentrations. The rs1619661 variant is on chromosome 10, 132 kilobase (kb) downstream from <em>CXCL12</em>, which encodes a chemokine, stromal cell-derived factor 1, that is expressed in cardiomyocytes and decreases calcium influx across the L-type Ca2+ channel. CONCLUSIONS: The findings suggest that biologically plausible genetic factors may alter susceptibility to PM10-associated QT prolongation in populations protected by the U.S. Environmental Protection Agency’s National Ambient Air Quality Standards. Independent replication and functional characterization are necessary to validate our findings. https://doi.org/10.1289/EHP347","journal":"UNC Libraries","year":2020,"id":138261,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5138,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":25010,"name":"Alex P. Reiner","orcid":"0000-0002-1427-4470","position":1,"is_corresponding":false},{"id":275264,"name":"James D. 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Méndez-Giráldez","orcid":null,"position":11,"is_corresponding":false},{"id":595338,"name":"Melanie Napier","orcid":null,"position":12,"is_corresponding":false},{"id":599720,"name":"Qing Duan","orcid":"0009-0002-5748-9065","position":13,"is_corresponding":false},{"id":291147,"name":"Colleen M. Sitlani","orcid":"0000-0001-7656-7482","position":14,"is_corresponding":false},{"id":277836,"name":"Zhu-Ming Zhang","orcid":"0000-0002-6013-1585","position":15,"is_corresponding":false},{"id":218550,"name":"Eric A. Whitsel","orcid":"0000-0003-4843-3641","position":16,"is_corresponding":false},{"id":274762,"name":"Christy L. 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