Jose D Vargas1, Ani Manichaikul2, Xin-Qun Wang3, Stephen S Rich4, Jerome I Rotter5, Wendy S Post6, Joseph F Polak7, Matthew J Budoff8, David A Bluemke9. 1. MedStar Health Research Institute, Georgetown University Hospital, Washington, DC, USA; National Institutes of Health, Radiology and Imaging Sciences, Bethesda, MD, USA. 2. Center for Public Health and Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA; Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA. 3. Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA. 4. Center for Public Health and Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA. 5. Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Population Sciences, Torrance, CA, USA. 6. Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA. 7. Department of Radiology, Tufts University School of Medicine, Boston, MA, USA. 8. Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, CA, USA. 9. National Institutes of Health, Radiology and Imaging Sciences, Bethesda, MD, USA. Electronic address: bluemked@cc.nih.gov.
Abstract
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. Published by Elsevier Ireland Ltd.
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. Published by Elsevier Ireland Ltd.
Entities:
Keywords:
Coronary calcium; Genetics; Intima-medial thickness; Single nucleotide polymorphism
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