Interactions between Polygenic Risk of Obesity and Dietary Factors on Anthropometric Outcomes: A Systematic Review and Meta-Analysis of Observational Studies

BACKGROUND: Diet is an important determinant of health and may moderate genetic susceptibility to obesity, but meta-analyses of available evidence are lacking. OBJECTIVES: This study aimed to systematically review and meta-analyze evidence on the moderating effect of diet on genetic susceptibility to obesity, assessed with polygenic risk scores (PRS). METHODS: A systematic search was conducted using MEDLINE, EMBASE, Web of Science, and the Cochrane Library to retrieve observational studies that examined PRS-diet interactions on obesity-related outcomes. Dietary exposures of interest included diet quality/dietary patterns and consumption of specific food and beverage groups. Random-effects meta-analyses were performed for pooled PRS- healthy eating index (HEI) interaction coefficients on body mass index (BMI) (on the basis of data from 4 cohort studies) and waist circumference (WC) (on the basis of data from 3 cohort studies). RESULTS: Out of 36 retrieved studies, 78% were conducted among European samples. Twelve out of 21 articles examining dietary indices/patterns, and 16 out of 21 articles examining food/beverage groups observed some significant PRS-diet interactions. However, within many articles, findings are inconsistent when testing different combinations of obesity PRS-dietary factors and outcomes. Nevertheless, higher HEI scores and adherence to plant-based dietary patterns emerged as the more prominent diet quality/patterns that moderated genetic susceptibility to obesity, whereas higher consumption of fruits and vegetables, and lower consumption of fried foods and sugar-sweetened beverages emerged as individual food/beverage moderators. Results from the meta-analysis suggest that a higher HEI attenuates genetic susceptibility on BMI (pooled PRS∗HEI coefficient: -0.08; 95% confidence interval (CI): -0.15, 0.00; P = 0.0392) and WC (-0.37; 95% CI: -0.60, -0.15; P = 0.0013). CONCLUSIONS: Current observational evidence suggests a moderating role of overall diet quality in polygenic risk of obesity. Future research should aim to identify genetic loci that interact with dietary exposures on anthropometric outcomes and conduct analyses among diverse ethnic groups. TRIAL REGISTRATION NUMBER: This study was registered at the International Prospective Register of Systematic Reviews as CRD42022312289.