Researchers analyzed 437,803 UK Biobank participants and found that polygenic scores—genetic risk profiles combining multiple variants—significantly modify how effectively fish oil supplements raise blood omega-3 levels. Participants with the lowest genetic scores (bottom 5%) showed 43% greater increases in circulating omega-3s from supplementation compared to those with the highest scores, with effect sizes ranging from 0.28 to 0.40 standard deviations. The genetic scores explained 5.3-11.1% of omega-3 variance across populations. This represents a significant advance toward precision nutrition, potentially explaining why omega-3 supplementation studies show inconsistent results—genetic background may determine individual response magnitude. The findings could revolutionize supplement recommendations, moving from one-size-fits-all dosing to genetically-informed protocols. However, this is a preprint awaiting peer review, so results may change during the review process. While the large sample size strengthens conclusions, the cross-sectional design limits causal inference. The discovery could transform how clinicians and consumers approach omega-3 supplementation, potentially improving cardiovascular and cognitive health outcomes through personalized dosing strategies based on genetic predisposition.