Association of a composite trait for anthropometrics, adiposity and energy expenditure with cardiometabolic diseases: An age-stratified cohort and genetic risk score analysis


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Association of a composite trait for anthropometrics, adiposity and energy expenditure with cardiometabolic diseases: An age-stratified cohort and genetic risk score analysis

Aim: Various anthropometric measures capture distinct as well as overlapping characteristics of an individual's body composition. To characterize independent body composition measures, we aimed to reduce easily-obtainable individual measures reflecting adiposity, anthropometrics and energy expenditure into fewer independent constructs, and to assess their potential sex- and age-specific relation with cardiometabolic diseases.

Methods: Analyses were performed within European ancestry participants from UK Biobank (N = 418,963, mean age 58.0 years, 56% women). Principal components (PC) analyses were used for the dimension reduction of 11 measures of adiposity, anthropometrics and energy expenditure. PCs were studied in relation to incident type 2 diabetes mellitus (T2D) and coronary artery disease (CAD). Multivariable-adjusted Cox regression analyses, adjusted for confounding factors, were performed in all and stratified by age. Genome-wide association st udies were performed in half of the cohort (N = 156,295) to identify genetic variants as instrumental variables. Genetic risk score analyses were performed in the other half of the cohort stratified by age of disease onset (N = 156,295).

Results: We identified two PCs, of which PC1 reflected lower overall adiposity (negatively correlated with all adiposity aspects) and PC2 reflected more central adiposity (mainly correlated with higher waist–hip ratio, but with lower total body fat) and increased height, collectively capturing 87.8% of the total variance. Similar to that observed in the multivariable-adjusted regression analyses, we found associations between the PC1 genetic risk score and lower risks of CAD and T2D [CAD cases <50 years, odds ratio: 0.91 (95% confidence interval 0.87, 0.94) per SD; T2D cases <50 years, odds ratio: 0.76 (0.72, 0.81)], which attenuated with higher age (p-values 8.13E-4 and 2.41E-6, respectively). No associations were found fo r PC2. Conclusions: The consistently observed weaker associations of the composite traits with cardiometabolic disease suggests the need for age-specific cardiometabolic disease prevention strategies. © 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Authors : Meulmeester F.L.; van Dijk K.W.; van Heemst D.; Noordam R.

Source : John Wiley and Sons Inc

Article Information

Year 2024
Type Article
DOI 10.1111/dom.15966
ISSN 14628902
Volume 26

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