(P29-013-24) The Moderating Role of Diet in Polygenic Risk of Obesity: A Systematic Review

Objectives: Diet is an important determinant of health and may moderate genetic susceptibility to obesity. This systematic review aimed to synthesize evidence related to interactions between polygenic risk scores (PRS) and diet on obesity outcomes. Diet exposures of interest included diet quality, dietary patterns, and food/beverage groups.

Methods: A systematic search was conducted using MEDLINE, EMBASE, Web of Science and Cochrane Library to identify cross-sectional and longitudinal studies published between 2012 and 2023 (PROSPERO CRD: 42022312289). Studies that assessed interactions between obesity-related PRS and diet exposures on anthropometric outcomes were evaluated. Study quality was assessed using the Newcastle Ottawa Scale (NOS) and a score assessing the methodological quality of gene-environment interaction studies.

Results: The search yielded 36 eligible publications, with 28 studies conducted among European samples and 8 studies among non-European samples. Weighted PRSs were commonly used in European samples, while unweighted PRS were more frequently used in non-European samples. According to the NOS, none of the studies were of low quality. However, when evaluating the methodological quality of gene-environment interaction studies, 11 studies were rated as low quality. About half (12/21) of studies that investigated diet quality or dietary patterns reported that higher diet quality or adherence to a healthful pattern attenuated associations between PRS and anthropometric outcomes. Approximately 75% (16/21) of studies that assessed food/beverage group consumption reported significant interactions. Higher intake of fruit and/or vegetables and lower intake of fried foods and soft drinks attenuated associations between PRS and anthropometric outcomes. Findings for alcohol-PRS interactions were mixed in terms of significance and directionality.

Conclusions: There is mixed evidence of interactions between diet exposures and polygenic risk of obesity on obesity-related outcomes, though certain food groups may be plausible factors. Further research addressing methodological limitations and PRS selection is needed to verify and better understand these potential interactions.

Funding Sources: Fond de Recherche du Quebec, Institute of Nutrition and Functional Foods