An examination of causal associations and shared risk factors for diabetes and cardiovascular diseases in the East Asian population: A Mendelian randomization study

BACKGROUND: One of the major contributors to disability and mortality among diabetics is cardiovascular disease (CVD), with coronary artery disease (CAD) as the most prevalent type. However, previous studies have provided controversial evidence linking diabetes to other types of CVDs, such as atrial fibrillation (AF). In addition, the risk factors that predispose people to the risk of diabetes and its complications differ across ethnicities, but the disease risk profiles in the East Asian population have been less investigated. METHODS: The causal association between type 2 diabetes (T2D) and two types of CVDs (i.e., AF and CAD) in the East Asian population was first studied using Mendelian randomization (MR) analyses. Next, we examined the causal effect of 49 traits on T2D and CAD to identify their separate and shared risk factors in East Asians. A causal mediation analysis was performed to examine the role of T2D in mediating the relationship between the identified shared risk factors and CAD. RESULTS: T2D was causally associated with CAD, but not AF, in East Asians. A screening of the risk factors indicated that six and 11 traits were causally associated with T2D and CAD, respectively, with suggestive levels of evidence. Alkaline phosphatase (ALP) was the only trait associated with both T2D and CAD, as revealed by the univariable MR analyses. Moreover, the causal association between ALP and CAD no longer existed after adjusting T2D as a covariable in the causal mediation study. CONCLUSION: Our study highlights the risk profiles in the East Asian population, which is important in formulating targeted therapies for T2D and CVDs in East Asians.