Genetic risk score is associated with T2DM and diabetes complications risks
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
36174902
DOI
10.1016/j.gene.2022.146921
PII: S0378-1119(22)00741-7
Knihovny.cz E-resources
- Keywords
- Complications, Diabetes, Gene score, Polymorphism,
- MeSH
- Genome-Wide Association Study MeSH
- Diabetes Mellitus, Type 2 * complications genetics MeSH
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics MeSH
- Genetic Predisposition to Disease MeSH
- Polymorphism, Single Nucleotide MeSH
- Diabetes Complications * MeSH
- Humans MeSH
- Risk Factors MeSH
- T Cell Transcription Factor 1 genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- FTO protein, human MeSH Browser
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
- T Cell Transcription Factor 1 MeSH
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 < 0.0001) were within the genes for TCF7L2 (transcription factor 7-like 2), FTO (fat mass and obesity associated protein) and ARAP1 (ankyrin repeat and PH domain 1). The T2DM-I subjects with uGRS values greater (Odds Ratio, 95 % Confidence Interval) than six had at least twice (2.00, 1.72-2.32) the risk of T2DM development (P < 0.0001), and these results were confirmed in the independent groups (T2DM-II 1.82, 1.45-2.27; T2DM-III 2.63, 2.11-3.27). The wGRS (>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.
Department of Pathophysiology Faculty of Medicine Masaryk University Brno Czech Republic
Diabetes Centre Institute for Clinical and Experimental Medicine Prague Czech Republic
Experimental Medicine Centre Institute for Clinical and Experimental Medicine Prague Czech Republic
Statistical Unit Institute for Clinical and Experimental Medicine Prague Czech Republic
References provided by Crossref.org
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