(P29-006-24) Polygenic Risk Scores and Meal Response in a Healthy Cohort of US Adults

Objectives: Genetics is an important factor affecting an individual’s metabolic response and disease risk. Polygenic risk scores (PRS) represent the cumulative genetic risk of all single nucleotide polymorphisms (SNPs) predisposing an individual to a particular phenotype. Using PRS generated from the USDA’s Nutritional Phenotyping Study, we first sought to assess the impact of genetic risk for BMI on the observed BMI in the cohort and if this genetic risk is similar between male and female participants. Secondly, we associated genetic risk for elevated fasting triglycerides with response to a Mixed Meal Tolerance test (MMTT).

Methods: The study contained 238 men and women between 18 and 64 years of age, with BMI from 18–40 kg/m2, who consented to genomewide genotyping and completed the MMTT as part of a broad nutritional phenotyping effort. Genome-wide genotyping data were assessed for quality participants and after highly related individuals were removed, mainly parent-child relationships, data from 231 participants remained for analysis. PRS were calculated using pgsc_calc v1.3.2 from the PGS Catalog, an open database of scores and their relevant metadata. BMI risk scores were developed from PGS ID PGS000027, while triglyceride risk scores were developed from PGS ID PGS002353. All analyses were completed in R Studio.

Results: PRS for obesity were associated with increased BMI in our cohort but sub-analysis by biological sex indicated that this association was not significant in females. Genetic risk was associated with increased post-prandial triglycerides 30 minutes following a high-fat high-sugar meal challenge in both males and females.

Conclusions: The use of PRS may be helpful to understand interindividual variation and sex differences for diet responses and diet dependent diseases. Further investigation into the dynamic changes following our metabolic meal challenge will help us understand how genetic risk influences post-prandial metabolism.

Funding Sources: USDA