Genetic Predisposition to Type 2 Diabetes and Risk of Subclinical Atherosclerosis and Cardiovascular Diseases Among 160,000 Chinese Adults

Diabetes. 2019 Nov;68(11):2155-2164. doi: 10.2337/db19-0224. Epub 2019 Aug 9.

Abstract

In observational studies, type 2 diabetes is associated with two- to fourfold higher risk of cardiovascular diseases (CVD). Using data from the China Kadoorie Biobank (CKB), we examined associations of genetically predicted type 2 diabetes with CVD among ∼160,000 participants to assess whether these relationships are causal. A type 2 diabetes genetic risk score (comprising 48 established risk variants) was associated with the presence of carotid plaque (odds ratio 1.17 [95% CI 1.05, 1.29] per 1 unit higher log-odds of type 2 diabetes; n = 6,819) and elevated risk of ischemic stroke (IS) (1.08 [1.02, 1.14]; n = 17,097), nonlacunar IS (1.09 [1.03, 1.16]; n = 13,924), and major coronary event (1.12 [1.02, 1.23]; n = 5,081). There was no significant association with lacunar IS (1.03 [0.91, 1.16], n = 3,173) or intracerebral hemorrhage (ICH) (1.01 [0.94, 1.10], n = 6,973), although effect estimates were imprecise. These associations were consistent with observational associations of type 2 diabetes with CVD in CKB (P for heterogeneity >0.3) and with the associations of type 2 diabetes with IS, ICH, and coronary heart disease in two-sample Mendelian randomization analyses based on summary statistics from European population genome-wide association studies (P for heterogeneity >0.2). In conclusion, among Chinese adults, genetic predisposition to type 2 diabetes was associated with atherosclerotic CVD, consistent with a causal association.

Publication types

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

MeSH terms

  • Adult
  • Atherosclerosis / epidemiology
  • Atherosclerosis / genetics*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • China / epidemiology
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Risk