A Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease

Nat Commun. 2015 May 28;6:7060. doi: 10.1038/ncomms8060.

Abstract

In observational studies, type-2 diabetes (T2D) is associated with an increased risk of coronary heart disease (CHD), yet interventional trials have shown no clear effect of glucose-lowering on CHD. Confounding may have therefore influenced these observational estimates. Here we use Mendelian randomization to obtain unconfounded estimates of the influence of T2D and fasting glucose (FG) on CHD risk. Using multiple genetic variants associated with T2D and FG, we find that risk of T2D increases CHD risk (odds ratio (OR)=1.11 (1.05-1.17), per unit increase in odds of T2D, P=8.8 × 10(-5); using data from 34,840/114,981 T2D cases/controls and 63,746/130,681 CHD cases/controls). FG in non-diabetic individuals tends to increase CHD risk (OR=1.15 (1.00-1.32), per mmol·per l, P=0.05; 133,010 non-diabetic individuals and 63,746/130,681 CHD cases/controls). These findings provide evidence supporting a causal relationship between T2D and CHD and suggest that long-term trials may be required to discern the effects of T2D therapies on CHD risk.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / genetics*
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Causality
  • Coronary Disease / epidemiology
  • Coronary Disease / genetics*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Glycated Hemoglobin A / genetics
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Mendelian Randomization Analysis
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Risk Factors

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human