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

• Published in: Cardiovascular diabetology Vol. 21; no. 1; p. 131
• Main Authors: Yun, Jae-Seung, Jung, Sang-Hyuk, Shivakumar, Manu, Xiao, Brenda, Khera, Amit V, Won, Hong-Hee, Kim, Dokyoon
• Format: Journal Article
• Language: English
• Published: England BioMed Central 14-07-2022; BMC
• Subjects: Biobanks; Biological Specimen Banks; Cardiac arrhythmia; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Cholesterol; Comorbidity; Congestive heart failure; Coronary artery; Coronary artery disease; Coronary vessels; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Eating behavior; Fibrillation; Genetic analysis; Genetic diversity; Genomes; Health behavior; Health care; Health risk assessment; Heart diseases; Humans; Interactive computer systems; Life Style; Lifestyle; Lifestyles; Lipoproteins; Metabolic health; Metabolic syndrome; Metabolism; Mortality; Obesity; Polygenic risk score; Prospective Studies; Quality control; Questionnaires; Risk Factors; Stroke; Type 2 diabetes; United Kingdom - epidemiology; Vascular diseases; Vein & artery diseases; United Kingdom; United Kingdom > UK; Polygenic risk score; Type 2 diabetes; Cardiovascular disease; Lifestyle; Metabolic health
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-022-01560-2

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.
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.
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).
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.