The Combined Effect of Polygenic Risk from FTO and ADRB2 Gene Variants, Odds of Obesity, and Post-Hipcref Diet Differences

Background: Computing polygenic risk scores (PRS) to predict the degree of risk for obesity may contribute to weight management programs strategically. Objectives: To investigate the combined effect of FTO rs9930501, rs9930506, and rs9932754 and ADRB2 rs1042713 and rs1042714 using PRS on (1) the odds of obesity and (2) post-intervention differences in dietary, anthropometric, and cardiometabolic parameters in response to high-protein calorie-restricted, high-vitamin E, high-fiber (Hipcref) diet intervention in Malaysian adults. Methods: Both a cross-sectional study ( n = 178) and a randomized controlled trial (RCT) ( n = 128) were conducted to test the aforementioned objectives. PRS was computed as the weighted sum of the risk alleles possessed by each individual participant. Participants were stratified into first (PRS 0–0.64), second (PRS 0.65–3.59), and third (PRS 3.60–8.18) tertiles. Results: The third tertile of PRS was associated with significantly higher odds of obesity: 2.29 (95% CI = 1.11–4.72, adjusted p = 0.025) compared to the first tertile. Indians (3.9 ± 0.3) had significantly higher PRS compared to Chinese (2.1 ± 0.4) ( p = 0.010). In the RCT, a greater reduction in high-sensitivity C-reactive protein (hsCRP) levels was found in second and third tertiles after Hipcref diet intervention compared to the control diet ( p interaction = 0.048). Conclusion: Higher PRS was significantly associated with increased odds of obesity. Individuals with higher PRS had a significantly greater reduction in hsCRP levels after Hipcref diet compared to the control diet.