Biological age acceleration and interaction with genetic predisposition in the risk of type 2 diabetes and coronary artery disease

Apr 29, 2025GeroScience

Faster biological aging and genetic risk linked to type 2 diabetes and heart disease

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Abstract

BA acceleration is positively associated with incident T2D and CAD, with hazard ratios for the highest risk groups reaching 6.89 for T2D and 2.80 for CAD.

BA provides a more accurate reflection of aging status compared to chronological age.
Individuals with greater BA acceleration had a higher risk of developing T2D and CAD.
Significant interactions between BA acceleration and genetic risk were observed, suggesting a compounded effect on disease risk.
The highest BA acceleration combined with polygenic risk score showed the strongest risk elevation for both T2D and CAD.
Incorporating BA measures and genetic risk into traditional risk models improved predictive performance for T2D and CAD.

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Biological age (BA), compared to chronological age, offers a more accurate reflection of aging status. In this prospective UK Biobank study, BA acceleration was measured using the Klemera-Doubal method BA (KDM-BA) and Phenotypic age (PhenoAge). Cox models estimated associations of BA acceleration with incident T2D (n = 271,885) and CAD (n = 270,054). Both additive and multiplicative interactions between BA acceleration and polygenic risk score (PRS) were examined. Predictive performance was assessed by adding BA, PRS, and their interactions to traditional risk models. BA acceleration was positively associated with incident T2D (HRfor KDM-BA: 2.38 [95% CI, 2.22-2.56]; HRfor PhenoAge: 1.85 [95% CI, 1.72-1.99]) and CAD (HRfor KDM-BA: 1.67 [95% CI, 1.58-1.76]; HRfor PhenoAge: 1.33 [95% CI, 1.27-1.39]). Significant multiplicative interactions were observed between BA acceleration and PRS (all P for multiplicative interaction ≤ 0.002). Individuals with highest BA acceleration and PRS had strongest risk elevation for T2D (HR for KDM-BA, 6.89 [95% CI, 6.03-7.87]; HR for PhenoAge, 6.28 [95% CI, 5.28-7.46]) and CAD (HR for KDM-BA, 2.80 [95% CI, 2.59-3.02]; HR for PhenoAge, 2.25 [95% CI, 2.07-2.45]). Additive interactions were observed for T2D with 18-28% of risk attributable to BA-genetic interaction. Adding BA measures and PRS to traditional risk models significantly improved prediction for both diseases (Δ C-statistic 0.024-0.034). In conclusion, BA acceleration was positively associated with incident T2D and CAD, especially in individuals with high genetic predisposition, and improved T2D and CAD prediction beyond traditional risk factors. Q4 vs Q1Q4 vs Q1Q4 vs Q1Q4 vs Q1

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Biological age acceleration and interaction with genetic predisposition in the risk of type 2 diabetes and coronary artery disease

Abstract

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