Assessment of Protein-Based Scores for Obesity Phenotypes in Predicting Major Adverse Cardiovascular Events and Type 2 Diabetes Across Ethnic Groups Open Access

Patel, Megha (Spring 2026)

Permanent URL: https://etd.library.emory.edu/concern/etds/mc87pr67j?locale=en
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Abstract

Protein-predicted scores (PPS) for body mass index (BMI), body fat percentage (BFP), and waist-to-hip ratio (WHR) are associated with incident major adverse cardiovascular events (MACE) and type 2 diabetes (T2D). However, the performance of the proteomic signatures has not been compared across ethnic groups. This thesis evaluated three obesity-related PPS, derived using LASSO regression from plasma proteomics data in UK Biobank participants, in relation to incident MACE and T2D among 31,167 participants, including 29,945 White, 766 Black, and 456 South Asian individuals. The associations were estimated using Fine and Gray competing risk models across adjusted models. Performance was assessed using C statistics in the overall cohort and ethnic-stratified subgroups. All three PPS were significantly associated with incident MACE in models adjusting for age, sex, and measured obesity, with associations attenuating after clinical adjustment. All scores were independently associated with incident T2D across all adjustment models. PPSWHR showed the most consistent associations for MACE and T2D. The combined PPS model including only age, sex and smoking had a C statistic of 0.68 for MACE, comparable to the PREVENT equation (0.69). For T2D, the C statistic of 0.77 was below the clinical model at 0.81. The associations and predictive performance of all models were more robust in White participants. PPSWHR was significantly associated with T2D in South Asian participants. C statistics for T2D were lower in Black (0.73) and South Asian (0.73) compared to White participants (0.79). These findings highlight the need to develop and validate proteomic risk tools in ethnically diverse cohorts.

Table of Contents

Literature Review............................................................................................................................ ii

Introduction ..................................................................................................................................... 1

Methods........................................................................................................................................... 2

Results ............................................................................................................................................. 4

Discussion ....................................................................................................................................... 6

Conclusion ...................................................................................................................................... 8

Public Health Implications .............................................................................................................. 8

Acknowledgements ......................................................................................................................... 9

Tables and Figures ........................................................................................................................ 10

Supplemental................................................................................................................................. 15

References ..................................................................................................................................... 18

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