Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes
Abstract Background Coronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European American...
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BMC
2017-12-01
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| Series: | BMC Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12863-017-0572-9 |
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| author | Jasmin Divers Nicholette D. Palmer Carl D. Langefeld W. Mark Brown Lingyi Lu Pamela J. Hicks S. Carrie Smith Jianzhao Xu James G. Terry Thomas C. Register Lynne E. Wagenknecht John S. Parks Lijun Ma Gary C. Chan Sarah G. Buxbaum Adolfo Correa Solomon Musani James G. Wilson Herman A. Taylor Donald W. Bowden John Jeffrey Carr Barry I. Freedman |
| author_facet | Jasmin Divers Nicholette D. Palmer Carl D. Langefeld W. Mark Brown Lingyi Lu Pamela J. Hicks S. Carrie Smith Jianzhao Xu James G. Terry Thomas C. Register Lynne E. Wagenknecht John S. Parks Lijun Ma Gary C. Chan Sarah G. Buxbaum Adolfo Correa Solomon Musani James G. Wilson Herman A. Taylor Donald W. Bowden John Jeffrey Carr Barry I. Freedman |
| author_sort | Jasmin Divers |
| collection | DOAJ |
| description | Abstract Background Coronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis. Results Single nucleotide polymorphisms (SNPs), rs11353135 (2q22.1), rs16879003 (6p22.3), rs5014012, rs58071836 and rs10244825 (all on chromosome 7), rs10918777 (9q31.2), rs13331874 (16p13.3) and rs4459623 (18q12.1) were associated with presence and/or quantity of CAC in the AA-DHS and JHS, with meta-analysis p-values ≤8.0 × 10−7. The strongest result in AA-DHS alone was rs6491315 in the 13q32.1 region (parameter estimate (SE) = −1.14 (0.20); p-value = 9.1 × 10−9). This GWAS peak replicated a previously reported AA-DHS CAC admixture signal (rs7492028, LOD score 2.8). Conclusions Genetic association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were detected in AAs with T2D from AA-DHS and replicated in the JHS. These data support a role for genetic variation on these chromosomes as contributors to CAC in AAs with T2D, as well as to variation in CAC between populations of African and European ancestry. |
| first_indexed | 2024-12-12T10:34:47Z |
| format | Article |
| id | doaj.art-89a2d93bbce542e69896590dcf94dfd6 |
| institution | Directory Open Access Journal |
| issn | 1471-2156 |
| language | English |
| last_indexed | 2024-12-12T10:34:47Z |
| publishDate | 2017-12-01 |
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| series | BMC Genetics |
| spelling | doaj.art-89a2d93bbce542e69896590dcf94dfd62022-12-22T00:27:16ZengBMCBMC Genetics1471-21562017-12-0118111310.1186/s12863-017-0572-9Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetesJasmin Divers0Nicholette D. Palmer1Carl D. Langefeld2W. Mark Brown3Lingyi Lu4Pamela J. Hicks5S. Carrie Smith6Jianzhao Xu7James G. Terry8Thomas C. Register9Lynne E. Wagenknecht10John S. Parks11Lijun Ma12Gary C. Chan13Sarah G. Buxbaum14Adolfo Correa15Solomon Musani16James G. Wilson17Herman A. Taylor18Donald W. Bowden19John Jeffrey Carr20Barry I. Freedman21Department of Biostatistical Sciences, Wake Forest School of Medicine, Medical Center BoulevardDepartment of Biochemistry, Wake Forest School of MedicineDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Medical Center BoulevardDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Medical Center BoulevardDepartment of Biostatistical Sciences, Wake Forest School of Medicine, Medical Center BoulevardCenter for Genomics and Personalized Medicine Research, Wake Forest School of MedicineCenter for Genomics and Personalized Medicine Research, Wake Forest School of MedicineCenter for Genomics and Personalized Medicine Research, Wake Forest School of MedicineDepartment of Radiology and Vanderbilt Center for Translation and Clinical Cardiovascular Research (VTRACC), Vanderbilt University School of MedicineDepartment of Pathology, Wake Forest School of MedicineDepartment of Epidemiology, Wake Forest School of MedicineDepartment of Internal Medicine–Section on Molecular Medicine, Wake Forest School of MedicineDepartment of Internal Medicine-Section on Nephrology, Wake Forest School of MedicineDepartment of Internal Medicine-Section on Nephrology, Wake Forest School of MedicineSchool of Public Health Initiative, Jackson State UniversityDepartment of MedicineDepartment of MedicineDepartment of Physiology and Biophysics, University of Mississippi Medical CenterMorehouse School of Medicine, Morehouse CollegeCenter for Genomics and Personalized Medicine Research, Wake Forest School of MedicineDepartment of Radiology and Vanderbilt Center for Translation and Clinical Cardiovascular Research (VTRACC), Vanderbilt University School of MedicineDepartment of Internal Medicine-Section on Nephrology, Wake Forest School of MedicineAbstract Background Coronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis. Results Single nucleotide polymorphisms (SNPs), rs11353135 (2q22.1), rs16879003 (6p22.3), rs5014012, rs58071836 and rs10244825 (all on chromosome 7), rs10918777 (9q31.2), rs13331874 (16p13.3) and rs4459623 (18q12.1) were associated with presence and/or quantity of CAC in the AA-DHS and JHS, with meta-analysis p-values ≤8.0 × 10−7. The strongest result in AA-DHS alone was rs6491315 in the 13q32.1 region (parameter estimate (SE) = −1.14 (0.20); p-value = 9.1 × 10−9). This GWAS peak replicated a previously reported AA-DHS CAC admixture signal (rs7492028, LOD score 2.8). Conclusions Genetic association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were detected in AAs with T2D from AA-DHS and replicated in the JHS. These data support a role for genetic variation on these chromosomes as contributors to CAC in AAs with T2D, as well as to variation in CAC between populations of African and European ancestry.http://link.springer.com/article/10.1186/s12863-017-0572-9African AmericansCoronary artery calcified atherosclerotic plaqueGenome-wide association studyCardiovascular diseaseType 2 diabetesGenetics |
| spellingShingle | Jasmin Divers Nicholette D. Palmer Carl D. Langefeld W. Mark Brown Lingyi Lu Pamela J. Hicks S. Carrie Smith Jianzhao Xu James G. Terry Thomas C. Register Lynne E. Wagenknecht John S. Parks Lijun Ma Gary C. Chan Sarah G. Buxbaum Adolfo Correa Solomon Musani James G. Wilson Herman A. Taylor Donald W. Bowden John Jeffrey Carr Barry I. Freedman Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes BMC Genetics African Americans Coronary artery calcified atherosclerotic plaque Genome-wide association study Cardiovascular disease Type 2 diabetes Genetics |
| title | Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes |
| title_full | Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes |
| title_fullStr | Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes |
| title_full_unstemmed | Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes |
| title_short | Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes |
| title_sort | genome wide association study of coronary artery calcified atherosclerotic plaque in african americans with type 2 diabetes |
| topic | African Americans Coronary artery calcified atherosclerotic plaque Genome-wide association study Cardiovascular disease Type 2 diabetes Genetics |
| url | http://link.springer.com/article/10.1186/s12863-017-0572-9 |
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