TY - JOUR
T1 - Common genetic variants and subclinical atherosclerosis
T2 - The Multi-Ethnic Study of Atherosclerosis (MESA)
AU - Vargas, Jose D.
AU - Manichaikul, Ani
AU - Wang, Xin Qun
AU - Rich, Stephen S.
AU - Rotter, Jerome I.
AU - Post, Wendy S.
AU - Polak, Joseph F.
AU - Budoff, Matthew J.
AU - Bluemke, David A.
N1 - Funding Information:
The authors thank the MESA investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.
Funding Information:
MESA and the MESA SHARe project are conducted and supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-001079 and UL1-TR-000040 from the National Heart, Lung, and Blood Institute (NHLBI, http://www.nhlbi.nih.gov ). MESA Family is conducted and supported in collaboration with MESA investigators; support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258, R01HL071259, M01-RR00425, UL1RR033176, and UL1TR000124. Funding for MESA SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The MESA study was approved by the institutional review boards of the participating institutions and participants provided informed consent prior to study participation. This manuscript was approved for submission by the Presentations and Publications Committee.
Publisher Copyright:
© 2015 Published by Elsevier Ireland Ltd.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Background and aims: Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds. Methods: The associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants [2329 Caucasians (EUA), 691 Chinese (CHN), 2482 African Americans (AFA), and 2012 Hispanic (HIS)] using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 × 10-4 (0.05/66). Results: In EUA there were significant associations for CAC with SNPs in 9p21 (rs1333049, P = 2 × 10-9; rs4977574, P = 4 × 10-9), COL4A1 (rs9515203, P = 9 × 10-6), and PHACTR1 (rs9349379, P = 4 × 10-4). In HIS, CAC was associated with SNPs in 9p21 (rs1333049, P = 8 × 10-5; rs4977574, P = 5 × 10-5), APOA5 (rs964184, P = 2 × 10-4), and ADAMTS7 (rs7173743, P = 4 × 10-4). There were no associations between CAC and 9p21 SNPs for AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN. Conclusion: Our results suggest some shared genetic architecture for sCVD across ethnic groups, while also underscoring the possibility of novel variants and/or pathways in risk of CVD in ethnically diverse populations.
AB - Background and aims: Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC) and carotid intima media thickness (CIMT) is associated with cardiovascular disease (CVD). Genome-Wide Association Studies (GWAS) of sCVD and CVD have focused primarily on Caucasian populations. We hypothesized that these associations may differ in populations from distinct genetic backgrounds. Methods: The associations between sCVD and 66 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) and MESA Family participants [2329 Caucasians (EUA), 691 Chinese (CHN), 2482 African Americans (AFA), and 2012 Hispanic (HIS)] using an additive model adjusting for CVD risk factors, with SNP significance defined by a Bonferroni-corrected p < 7.6 × 10-4 (0.05/66). Results: In EUA there were significant associations for CAC with SNPs in 9p21 (rs1333049, P = 2 × 10-9; rs4977574, P = 4 × 10-9), COL4A1 (rs9515203, P = 9 × 10-6), and PHACTR1 (rs9349379, P = 4 × 10-4). In HIS, CAC was associated with SNPs in 9p21 (rs1333049, P = 8 × 10-5; rs4977574, P = 5 × 10-5), APOA5 (rs964184, P = 2 × 10-4), and ADAMTS7 (rs7173743, P = 4 × 10-4). There were no associations between CAC and 9p21 SNPs for AFA and CHN. Fine mapping of the 9p21 region revealed SNPs with robust associations with CAC in EUA and HIS but no significant associations in AFA and CHN. Conclusion: Our results suggest some shared genetic architecture for sCVD across ethnic groups, while also underscoring the possibility of novel variants and/or pathways in risk of CVD in ethnically diverse populations.
KW - Coronary calcium
KW - Genetics
KW - Intima-medial thickness
KW - Single nucleotide polymorphism
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U2 - 10.1016/j.atherosclerosis.2015.11.034
DO - 10.1016/j.atherosclerosis.2015.11.034
M3 - Article
C2 - 26789557
AN - SCOPUS:84954287447
SN - 0021-9150
VL - 245
SP - 230
EP - 236
JO - Atherosclerosis
JF - Atherosclerosis
ER -