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• W1992875983 abstract "Objective— Carotid intima-media thickness (cIMT), a marker for atherosclerosis, is affected by smoking and has substantial interindividual variation. We sought to identify the genetic moderators influencing the effect of smoking on cIMT. Approach and Results— With a multistage design using 722 379 single nucleotide polymorphisms (SNP), a genome-wide interaction study was performed in a discovery sample of 669 Hispanics, followed by replication in 589 subjects (264 Hispanics, 172 non-Hispanic blacks, 153 non-Hispanic whites). Assuming an additive genetic model, regression analysis was performed to test for smoking–SNP interaction on cIMT while controlling for age, sex, and the top 3 principal components of ancestry. The strongest interaction in Hispanics was found with a synonymous splicing SNP (rs3751383) in exon 9 of RCBTB1 ( P =2.5e −6 in discovery sample; P =0.01 in the Hispanic replication sample; P <8.8e −9 in the combined Hispanic sample). Stratification analysis in the combined Hispanic sample showed that smoking had no effect on cIMT among rs3751383 G homozygote ( P =0.15), a moderate effect among rs3751383 heterozygote ( P =0.01), and a strong effect among rs3751383 A homozygote ( P =2.1e −7 ). A consistent trend was observed in the non-Hispanic white and black data sets, leading to an interaction effect of P <2.9e −9 in the meta-analysis of all 1258 subjects. Conclusions— Our study represents the first genome-wide smoking–SNP interaction study of cIMT and identifies RCBTB1 as a modifier of the smoking effect on cIMT. Testing for gene–environment interactions can help uncover genetic factors that contribute to the interindividual variation in response to the same environmental exposure." @default.
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• W1992875983 date "2014-01-01" @default.
• W1992875983 modified "2023-10-16" @default.
• W1992875983 title "Genome-Wide Interaction Study Identifies RCBTB1 as a Modifier for Smoking Effect on Carotid Intima-Media Thickness" @default.
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• W1992875983 doi "https://doi.org/10.1161/atvbaha.113.302706" @default.
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