title: Admixture mapping of coronary artery calcified plaque in African Americans with type 2 diabetes mellitus.
abstract: 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.
  
  
  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.
authors.affiliation: Departments of Biostatistical Sciences,Wake Forest School of Medicine, Winston-Salem, NC 27157-1053, USA.
authors.forename: Jasmin
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authors.lastname: Divers
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.forename: Lingyi
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authors.lastname: Lu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.forename: J Jeffrey
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authors.lastname: Carr
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: R Caresse
authors.initials: RC
authors.lastname: Hightower
authors.forename: S Carrie
authors.initials: SC
authors.lastname: Smith
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Xu
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cox
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hruska
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.forename: Gerardo
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authors.lastname: Heiss
authors.forename: Michael A
authors.initials: MA
authors.lastname: Province
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.forename: Y-D Ida
authors.initials: YD
authors.lastname: Chen
authors.forename: Walter
authors.initials: W
authors.lastname: Palmas
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Christina L
authors.initials: CL
authors.lastname: Wassel
authors.forename: Alain G
authors.initials: AG
authors.lastname: Bertoni
authors.forename: David M
authors.initials: DM
authors.lastname: Herrington
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic; D020641:Polymorphism, Single Nucleotide