Genetic epidemiology of subclinical cardiovascular disease in the diabetes heart study

Ann Hum Genet. 2008 Sep;72(Pt 5):598-610. doi: 10.1111/j.1469-1809.2008.00446.x. Epub 2008 Apr 29.

Abstract

A genome-wide linkage scan of 357 European American (EA) and 72 African American (AA) pedigrees multiplex for type 2 diabetes mellitus (T2DM) was performed with multipoint nonparametric QTL linkage analysis. Four subclinical measures of cardiovascular disease (CVD): coronary artery (CCP), carotid artery (CarCP), and abdominal aortic calcified plaque (AACP) and carotid artery intima-media thickness (IMT) were mapped. Analyses were adjusted for age, gender, body mass index, and (if appropriate) ethnicity and diabetes status. Evidence for linkage was observed in EA T2DM subjects to CarCP near 16p13 (LOD=4.39 at 8.4 cM; P = 0.00001). When all EA subjects were included, the LOD score was 2.52, suggesting an amplification of the linkage by diabetes. Linkage analysis of a principal components measure of vascular calcium (LOD = 3.85 at 9.3 cM on 16p in EA T2DM subjects) and bivariate analysis of CarCP X IMT (LOD = 3.77 at 9.3 cM on 16p in EA T2DM subjects) were consistent with this linkage. In addition, evidence for linkage was observed with CCP near D15S1515 (LOD = 2.34) in EAs. Additional loci on chromosomes 1, 2, 7, 10, 13, and 21 had LODs > 2.0. The identification of trait-determining polymorphisms underlying these linkages will help delineate risk factors for CVD in T2DM and the general population.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Black or African American / genetics
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / diagnostic imaging
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / genetics
  • DNA / genetics
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genotype
  • Humans
  • Lod Score
  • Male
  • Molecular Epidemiology
  • North Carolina / epidemiology
  • Pedigree
  • Quantitative Trait Loci
  • Tomography, X-Ray Computed
  • White People / genetics

Substances

  • DNA