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Genetic risk score is associated with T2DM and diabetes complications risks

JA. Hubacek, L. Dlouha, V. Adamkova, D. Dlouha, L. Pacal, K. Kankova, D. Galuska, V. Lanska, J. Veleba, T. Pelikanova

. 2023 ; 849 (-) : 146921. [pub] 20220926

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc22031990

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.

Citace poskytuje Crossref.org

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$a BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prototypical complex disease with polygenic architecture playing an important role in determining susceptibility to develop the disease (and its complications) in subjects exposed to modifiable lifestyle factors. A current challenge is to quantify the degree of the individual's genetic risk using genetic risk scores (GRS) capturing the results of genome-wide association studies while incorporating possible ethnicity- or population-specific differences. METHODS: This study included three groups of T2DM (T2DM-I, N = 1,032; T2DM-II, N = 353; and T2DM-III, N = 399) patients and 2,481 diabetes-free subjects. The status of the microvascular and macrovascular diabetes complications were known for the T2DM-I patients. Overall, 21 single nucleotide polymorphisms (SNPs) were analyzed, and selected subsets were used to determine the GRS (both weighted - wGRS and unweighted - uGRS) for T2DM risk predictions (6 SNPs) and for predicting the risks of complications (7 SNPs). RESULTS: The strongest T2DM markers (P < 0.0001) were within the genes for TCF7L2 (transcription factor 7-like 2), FTO (fat mass and obesity associated protein) and ARAP1 (ankyrin repeat and PH domain 1). The T2DM-I subjects with uGRS values greater (Odds Ratio, 95 % Confidence Interval) than six had at least twice (2.00, 1.72-2.32) the risk of T2DM development (P < 0.0001), and these results were confirmed in the independent groups (T2DM-II 1.82, 1.45-2.27; T2DM-III 2.63, 2.11-3.27). The wGRS (>0.6) further improved (P < 0.000001) the risk estimations for all three T2DM groups. The uGRS was also a significant predictor of neuropathy (P < 0.0001), nephropathy (P < 0.005) and leg ischemia (P < 0.0005). CONCLUSIONS: If carefully selected and specified, GRS, both weighted and unweighted, could be significant predictors of T2DM development, as well as the diabetes complications development.
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$a Dlouha, Lucie $u Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic
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$a Adamkova, Vera $u Department of Preventive Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Czech Technical University of Prague, Faculty of Biomedical Engineering, Prague, Czech Republic
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$a Dlouha, Dana $u Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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$a Pacal, Lukas $u Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Kankova, Katerina $u Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Galuska, David $u Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Lanska, Vera $u Statistical Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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$a Veleba, Jiri $u Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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$a Pelikanova, Terezie $u Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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