TY - JOUR
T1 - Admixture mapping of coronary artery calcified plaque in African Americans with type 2 diabetes mellitus
AU - Divers, Jasmin
AU - Palmer, Nicholette D.
AU - Lu, Lingyi
AU - Register, Thomas C.
AU - Carr, J. Jeffrey
AU - Hicks, Pamela J.
AU - Hightower, R. Caresse
AU - Smith, S. Carrie
AU - Xu, Jianzhao
AU - Cox, Amanda J.
AU - Hruska, Keith A.
AU - Bowden, Donald W.
AU - Lewis, Cora E.
AU - Heiss, Gerardo
AU - Province, Michael A.
AU - Borecki, Ingrid B.
AU - Kerr, Kathleen F.
AU - Chen, Y. D.Ida
AU - Palmas, Walter
AU - Rotter, Jerome I.
AU - Wassel, Christina L.
AU - Bertoni, Alain G.
AU - Herrington, David M.
AU - Wagenknecht, Lynne E.
AU - Langefeld, Carl D.
AU - Freedman, Barry I.
PY - 2013/2
Y1 - 2013/2
N2 - Background-The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping may be informative for identifying genetic variants associated with subclinical cardiovascular disease. Methods and Results-Admixture mapping of CAC was performed in 1040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study, Multi-Ethnic Study of Atherosclerosis and Family Heart Study using the Illumina custom ancestry informative marker panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each ancestry informative marker, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each ancestry informative marker using these probabilities and CAC, accounting for global ancestry, age, sex, and study. Markers on 1p32.3 in the GLIS1 gene (rs6663966, logarithm of odds [LOD]=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0), and 11q25 in the OPCML gene (rs6590705, LOD=3.4) had statistically significant LOD scores, whereas markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1350 African Americans without diabetes mellitus and 2497 diabetic European Americans from Multi-Ethnic Study of Atherosclerosis and the Diabetes Heart Study. Conclusions-Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical cardiovascular disease.
AB - Background-The presence and severity of coronary artery calcified plaque (CAC) differs markedly between individuals of African and European descent, suggesting that admixture mapping may be informative for identifying genetic variants associated with subclinical cardiovascular disease. Methods and Results-Admixture mapping of CAC was performed in 1040 unrelated African Americans with type 2 diabetes mellitus from the African American-Diabetes Heart Study, Multi-Ethnic Study of Atherosclerosis and Family Heart Study using the Illumina custom ancestry informative marker panel. All cohorts obtained computed tomography scanning of the coronary arteries using identical protocols. For each ancestry informative marker, the probability of inheriting 0, 1, and 2 copies of a European-derived allele was determined. Linkage analysis was performed by testing for association between each ancestry informative marker using these probabilities and CAC, accounting for global ancestry, age, sex, and study. Markers on 1p32.3 in the GLIS1 gene (rs6663966, logarithm of odds [LOD]=3.7), 1q32.1 near CHIT1 (rs7530895, LOD=3.1), 4q21.2 near PRKG2 (rs1212373, LOD=3.0), and 11q25 in the OPCML gene (rs6590705, LOD=3.4) had statistically significant LOD scores, whereas markers on 8q22.2 (rs6994682, LOD=2.7), 9p21.2 (rs439314, LOD=2.7), and 13p32.1 (rs7492028, LOD=2.8) manifested suggestive evidence of linkage. These regions were uniformly characterized by higher levels of European ancestry associating with higher levels or odds of CAC. Findings were replicated in 1350 African Americans without diabetes mellitus and 2497 diabetic European Americans from Multi-Ethnic Study of Atherosclerosis and the Diabetes Heart Study. Conclusions-Fine mapping these regions will likely identify novel genetic variants that contribute to CAC and clarify racial differences in susceptibility to subclinical cardiovascular disease.
KW - Admixture mapping
KW - Ancestry
KW - Cardiovascular disease risk factors
KW - Type 2 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=84878031443&partnerID=8YFLogxK
U2 - 10.1161/CIRCGENETICS.112.964114
DO - 10.1161/CIRCGENETICS.112.964114
M3 - Review article
C2 - 23233742
AN - SCOPUS:84878031443
SN - 1942-325X
VL - 6
SP - 97
EP - 105
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
IS - 1
ER -