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Session: Personalizing Nutrition - Genetics and Dietary Pattern interactions (Poster Theater Flash Session 2)

(PTFS02-05-23) Gene-Level Gene-Mediterranean Diet Interactions Influencing Chronic Inflammation in 137,000 UK Biobank Participants

Saturday, July 22, 2023

2:51 PM – 2:55 PM ET

Location: Fairfax

Presenting Author(s)

Kenneth E. Westerman, PhD

Instructor
Massachusetts General Hospital
Washington, District of Columbia, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

AM

Alisa K. Manning, PhD

Massachusetts General Hospital
Boston, Massachusetts, United States

Disclosure(s):

Kenneth E. Westerman, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Adherence to a Mediterranean diet pattern reduces cardiometabolic risk, partially by reducing chronic inflammation. However, there is heterogeneity in the long-term inflammatory response to dietary changes, likely due in part to genetic factors. Using a genome-wide interaction study (GWIS) approach, we sought to find genes contributing to this heterogeneity in the Mediterranean diet-inflammation relationship.

Methods: We studied an unrelated, multi-ancestry sample from the UK Biobank cohort who completed at least one 24-hour diet questionnaire, had measured high-sensitivity C-reactive protein (hsCRP; a marker of chronic inflammation), and were free of major disease (N = 136,880). We calculated a nine-item Mediterranean diet score (MDS) based on food group and nutrient intakes. We conducted nine GWIS to test for significant variant-diet interactions (one per MDS component). We generated gene-level results using MAGMA, which tests for enrichment of genetic signal at variants near each of 18,249 genes. Genome-wide sensitivity models used food frequency questionnaire-based estimates of oily and non-oily fish intake (N = 362,380).

Results: In genotype-free models, MDS and its components showed strong inverse relationships with hsCRP; for fish and nuts, these relationships were stronger when modeling them as binary (consumers vs. non-consumers) rather than continuous. In the primary GWIS, no significant variant-level interactions were observed, but six gene-level tests (four for fish and two for nuts) passed a Bonferroni threshold of p = 2.7x10^-6. For example, MUCL1, which has been linked to inflammatory diseases such as eczema, modified the fish intake-hsCRP relationship. This MUCL1 interaction was robust using an alternative inflammation biomarker based on blood cell counts; p = 0.004). It also retained some signal when using oily (p = 0.059) but not non-oily (p = 0.82) fish intakes, suggesting a specific importance of fatty acids such as DHA and EPA in this interaction.

Conclusions: Our gene-based GWIS analysis prioritized MUCL1 and other genes that may modify the diet-inflammation relationship. It further demonstrates key strategies to improve gene-diet interaction studies, including preprocessing decisions based on preliminary genotype-free models and gene-based aggregation for improved statistical power.

Funding Sources: NIDDK