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. 2022 Jul 14;21(1):131.
doi: 10.1186/s12933-022-01560-2.

Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study

Jae-Seung Yun #  1   2 , Sang-Hyuk Jung #  1   3   4 , Manu Shivakumar  1   4 , Brenda Xiao  1   5 , Amit V Khera  6 , Hong-Hee Won #  7   8 , Dokyoon Kim #  9   10
Affiliations

Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study

Jae-Seung Yun et al. Cardiovasc Diabetol. .

Abstract

Background: Few studies have examined associations between genetic risk for type 2 diabetes (T2D), lifestyle, clinical risk factors, and cardiovascular disease (CVD). We aimed to investigate the association of and potential interactions among genetic risk for T2D, lifestyle behavior, and metabolic risk factors with CVD.

Methods: A total of 345,217 unrelated participants of white British descent were included in analyses. Genetic risk for T2D was estimated as a genome-wide polygenic risk score constructed from > 6 million genetic variants. A favorable lifestyle was defined in terms of four modifiable lifestyle components, and metabolic health status was determined according to the presence of metabolic syndrome components.

Results: During a median follow-up of 8.9 years, 21,865 CVD cases (6.3%) were identified. Compared with the low genetic risk group, participants at high genetic risk for T2D had higher rates of overall CVD events, CVD subtypes (coronary artery disease, peripheral artery disease, heart failure, and atrial fibrillation/flutter), and CVD mortality. Individuals at very high genetic risk for T2D had a 35% higher risk of CVD than those with low genetic risk (HR 1.35 [95% CI 1.19 to 1.53]). A significant gradient of increased CVD risk was observed across genetic risk, lifestyle, and metabolic health status (P for trend > 0.001). Those with favorable lifestyle and metabolically healthy status had significantly reduced risk of CVD events regardless of T2D genetic risk. This risk reduction was more apparent in young participants (≤ 50 years).

Conclusions: Genetic risk for T2D was associated with increased risks of overall CVD, various CVD subtypes, and fatal CVD. Engaging in a healthy lifestyle and maintaining metabolic health may reduce subsequent risk of CVD regardless of genetic risk for T2D.

Keywords: Cardiovascular disease; Lifestyle; Metabolic health; Polygenic risk score; Type 2 diabetes.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
A CVD incidence rates according to the risk groups of T2D PRS. B Hazard plot for CVD risk according to the risk group of T2D PRS. T2D PRS risk groups: low (0–19th percentile), intermediate (20–79th percentile), high (80–98th percentile), and very high (99th percentile). Error bars represent 95% CI of estimated cumulative incidence. CVD: cardiovascular disease; T2D: type 2 diabetes; PRS: polygenic risk score; HR: hazard ratio; CI: confidence interval
Fig. 2
Fig. 2
Hazard ratio for overall and subtypes of cardiovascular outcome according to T2D PRS risk group. CVD: cardiovascular disease; T2D: type 2 diabetes; PRS: polygenic risk score; HR: hazard ratio; CI: confidence interval; SD: standard deviation
Fig. 3
Fig. 3
Forest plot for cardiovascular disease risk reduced by metabolic health status and lifestyle behavior in high and low genetic risk group for type 2 diabetes. Participants were categorized according to type 2 diabetes genetic risk into the following two subgroups: low (0–80th percentile), high (80–99th percentile). MetS, metabolic syndrome; HR, hazard ratio; CI, confidence interval
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