Abstrakt
Background: Type 2 diabetes mellitus (T2DM) is a prototypical complex disease with polygenic architecture playing an important role in determining susceptibility to develop the disease (and its complications) in subjects exposed to modifiable lifestyle factors. A current challenge is to quantify the degree of the individual's genetic risk using genetic risk scores (GRS) capturing the results of genome-wide association studies while incorporating possible ethnicity- or population-specific differences.
Methods: This study included three groups of T2DM (T2DM-I, N = 1,032; T2DM-II, N = 353; and T2DM-III, N = 399) patients and 2,481 diabetes-free subjects. The status of the microvascular and macrovascular diabetes complications were known for the T2DM-I patients.
Overall, 21 single nucleotide polymorphisms (SNPs) were analyzed, and selected subsets were used to determine the GRS (both weighted - wGRS and unweighted - uGRS) for T2DM risk predictions (6 SNPs) and for predicting the risks of complications (7 SNPs). Results: The strongest T2DM markers (P 0.6) further improved (P < 0.000001) the risk estimations for all three T2DM groups.
The uGRS was also a significant predictor of neuropathy (P < 0.0001), nephropathy (P < 0.005) and leg ischemia (P < 0.0005). Conclusions: If carefully selected and specified, GRS, both weighted and unweighted, could be significant predictors of T2DM development, as well as the diabetes complications development.