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Genetic Risk Score Enhances Coronary Artery Disease Risk Prediction in Individuals With Type 1 Diabetes

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posted on 13.01.2022, 15:35 authored by Raija Lithovius, Anni A. Antikainen, Stefan Mutter, Erkka Valo, Carol Forsblom, Valma Harjutsalo, Niina Sandholm, Per-Henrik Groop, the FinnDiane Study Group
OBJECTIVE Individuals with type 1 diabetes are at a high lifetime risk of coronary artery disease (CAD) calling for early interventions. This study explores the use of a genetic risk score (GRS) for CAD risk prediction, compares it to established clinical markers and investigates its performance according to the age and pharmacological treatment.

RESEARCH DESIGN AND METHODS This study in 3,295 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy Study (467 incident CAD, 14.8 years follow-up) employed three risk scores: a GRS, a validated clinical score and their combined score. Hazard ratios (HR) were calculated with Cox regression and model performances compared with Harrel’s C-index.

RESULTS A HR of 6.7 for CAD was observed between the highest and the lowest 5th percentile of the GRS (P=1.8×10-6). The performance of GRS (C-index [C] 0.562) was similar to HbA1c (C=0.563, p-value for difference 0.96), HDL (C=0.571, P=0.6) and total cholesterol (C=0.594, P=0.1). The GRS was not correlated with the clinical score (r=-0.013, P=0.5). The combined score outperformed the clinical score (C=0.813 vs C=0.820, P=0.003). The GRS performed better in individuals below the median age (38.6 years) compared to those above (C=0.637 vs C=0.546).

CONCLUSIONS A GRS identified individuals at high risk of CAD and worked better in younger individuals. GRS was also an independent risk factor for CAD with a predictive power comparable to that of HbA1c, HDL and total cholesterol and, when incorporated into a clinical model, modestly improved the predictions. The GRS promises early risk stratification in clinical practice by enhancing the prediction of CAD.

Funding

This study was supported by grants from Finnish Diabetes Research Foundation (Diabetestutkimussäätiö) and the Finnish Foundation for Cardiovascular Research (Sydäntutkimussäätiö). The FinnDiane study was supported by grants from Folkhälsan Research Foundation, Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, Helsinki University Central Hospital Research Funds (EVO), Novo Nordisk Foundation (NNFOC0013659), and Academy of Finland (#299200 and #316664). Genotyping of the FinnDiane GWAS data was funded by the Juvenile Diabetes Research Foundation (JDRF) as part of the Diabetic Nephropathy Collaborative Research Initiative (DNCRI; Grant 17-2013-7), with GWAS quality control and imputation performed at University of Virginia.

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