title: Genetic susceptibility to coronary heart disease in type 2 diabetes: 3 independent studies.
abstract: OBJECTIVE
  The aim of this study was to evaluate whether coronary heart disease (CHD)-susceptibility loci identified by genome-wide association studies of the general population also contribute to CHD in type 2 diabetes.
  
  
  BACKGROUND
  No study has examined the effects of these genetic variants on CHD in diabetic patients.
  
  
  METHODS
  We genotyped 15 genetic markers of 12 loci in 3 studies of diabetic patients: the prospective Nurses' Health Study (309 CHD cases, and 544 control subjects) and Health Professional Follow-up Study (345 CHD cases, and 451 control subjects) and the cross-sectional Joslin Heart Study (422 CHD cases, and 435 control subjects).
  
  
  RESULTS
  Five single-nucleotide polymorphisms, rs4977574 (CDKN2A/2B), rs12526453 (PHACTR1), rs646776 (CELSR2-PSRC1-SORT1), rs2259816 (HNF1A), and rs11206510 (PCSK9) showed directionally consistent associations with CHD in the 3 studies, with combined odds ratios (ORs) ranging from 1.17 to 1.25 (p = 0.03 to 0.0002). None of the other single-nucleotide polymorphisms reached significance in individual or combined analyses. A genetic risk score (GRS) was created by combining the risk alleles of the 5 significantly associated loci. The OR of CHD/GRS unit was 1.19 (95% confidence interval: 1.13 to 1.26; p < 0.0001). Individuals with GRS ≥8 (19% of diabetic subjects) had almost a 2-fold increase in CHD risk (OR: 1.94, 95% confidence interval: 1.60 to 2.35) as compared with individuals with GRS ≤5 (30% of diabetic subjects). Prediction of CHD was significantly improved (p < 0.001) when the GRS was added to a model including clinical predictors in the combined samples.
  
  
  CONCLUSIONS
  Our results illustrate the consistency and differences in the determinants of genetic susceptibility to CHD in diabetic patients and the general populations.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. nhlqi@channing.harvard.edu
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.forename: Layla
authors.initials: L
authors.lastname: Parast
authors.forename: Tianxi
authors.initials: T
authors.lastname: Cai
authors.forename: Christine
authors.initials: C
authors.lastname: Powers
authors.forename: Ernest V
authors.initials: EV
authors.lastname: Gervino
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hauser
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Alessandro
authors.initials: A
authors.lastname: Doria
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018570:Risk Assessment