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Polygenic predisposition modifies the associations of fish oil supplementation with circulating omega-3 fatty acids: a cross-sectional gene-diet interaction study in UK Biobank

Xu H, Yu G, Lu Y, Fuller H, Song S, Shen Y, Chiang CWK, Darst BF et al.

2026

437,803 participants

Abstract

Background: Several genetic variants have been identified to modify the effects of fish oil supplementation (FOS) on increasing circulating omega-3 fatty acids, but it remains unexplored whether polygenic predisposition to low circulating omega-3 fatty acids modifies these effects.

Objective: To test if polygenic scores (PGS) for circulating omega-3 fatty acids modify the associations of FOS with corresponding circulating concentrations.

Methods: We developed PGS models for absolute circulating concentrations of total omega-3 fatty acids (Omega-3), docosahexaenoic acid (DHA), and their relative percentages in total fatty acids (Omega-3% and DHA%), using a multi-ethnic genome-wide association study (N=136,016). PGS models were validated in 437,803 UK Biobank participants of European (EUR), Central/South Asian (CSA), African, and East Asian genetic ancestries. Linear models tested PGS-by-FOS interactions on corresponding observed circulating concentrations. Discovery analysis was performed separately in 237,380 EUR participants and each non-EUR group. Replication analyses were performed using oily fish intake and in another 178,935 EUR participants.

Results: In EUR participants, PGS explained 5.3-11.1% of the phenotypic variance, and significant PGS-by-FOS interactions were detected across all four circulating omega-3 traits. Among participants in the bottom 5% of the PGS distribution, FOS was significantly associated with a 0.40 SD (95% CI: 0.39–0.44) increase in Omega-3.…

How strong is the evidence?

Evidence Hub reads this as a cross-sectional. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 437,803 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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