Genome-wide interaction study identifies RCBTB1 as a modifier for smoking effect on carotid intima-media thickness

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7 Citations (Scopus)

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 in discovery sample; P=0.01 in the Hispanic replication sample; P<8.8e 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). A consistent trend was observed in the non-Hispanic white and black data sets, leading to an interaction effect of P<2.9e 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.

Original languageEnglish
Pages (from-to)219-225
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2014

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Carotid Intima-Media Thickness
Hispanic Americans
Smoking
Genome
Single Nucleotide Polymorphism
Homozygote
Gene-Environment Interaction
Genetic Models
Environmental Exposure
Heterozygote
Meta-Analysis
Exons
Atherosclerosis
Regression Analysis

Keywords

  • Carotid arteries
  • Carotid intima-media thickness
  • Hispanic Americans

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{74df4b3c45a04430ba2676d0a09835ae,
title = "Genome-wide interaction study identifies RCBTB1 as a modifier for smoking effect on carotid intima-media thickness",
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 in discovery sample; P=0.01 in the Hispanic replication sample; P<8.8e 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). A consistent trend was observed in the non-Hispanic white and black data sets, leading to an interaction effect of P<2.9e 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.",
keywords = "Carotid arteries, Carotid intima-media thickness, Hispanic Americans",
author = "Liyong Wang and Tatjana Rundek and Ashley Beecham and Barry Hudson and Blanton, {Susan H} and Hongyu Zhao and Sacco, {Ralph L} and Chuanhui Dong",
year = "2014",
month = "1",
day = "1",
doi = "10.1161/ATVBAHA.113.302706",
language = "English",
volume = "34",
pages = "219--225",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Genome-wide interaction study identifies RCBTB1 as a modifier for smoking effect on carotid intima-media thickness

AU - Wang, Liyong

AU - Rundek, Tatjana

AU - Beecham, Ashley

AU - Hudson, Barry

AU - Blanton, Susan H

AU - Zhao, Hongyu

AU - Sacco, Ralph L

AU - Dong, Chuanhui

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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 in discovery sample; P=0.01 in the Hispanic replication sample; P<8.8e 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). A consistent trend was observed in the non-Hispanic white and black data sets, leading to an interaction effect of P<2.9e 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.

AB - 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 in discovery sample; P=0.01 in the Hispanic replication sample; P<8.8e 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). A consistent trend was observed in the non-Hispanic white and black data sets, leading to an interaction effect of P<2.9e 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.

KW - Carotid arteries

KW - Carotid intima-media thickness

KW - Hispanic Americans

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U2 - 10.1161/ATVBAHA.113.302706

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