Associations of vegetarianism with circulating lipids across varying genetic capacity: a cross-sectional Polygenic Score-by-Vegetarianism interaction study in UK Biobank

Background: Circulating lipid levels are influenced by both genetic and environmental factors. While vegetarianism has been linked to improved lipid profiles, it remains unclear whether these beneficial effects persist across individuals with varying genetic capacity for lipid metabolism. Objective: We hypothesized that genetic capacity and vegetarianism interact to influence the circulating levels of four lipids, including total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG). Methods: Our study included UK Biobank participants of European (EUR, n = 182,300), Central/South Asian (CSA, n = 2,627), African (n = 2,143), and East Asian (n = 1,031) ancestry. Utilizing polygenic scores (PGS) for four circulating lipids, we employed multivariable regression models to assess PGS-by-vegetarianism interactions for each lipid. Results: Vegetarianism is associated with reduced levels of TC, LDL cholesterol, and HDL cholesterol, and with elevated levels of TG in the EUR cohort (p-value < 0.001). The same significant association patterns were observed for HDL cholesterol and TG in the CSA cohort. We did not detect significant PGS-by-vegetarianism interactions for any lipid traits (Interaction p-value > 0.05). There is a lack of evidence supporting that PGS modifies the associations between vegetarianism and lipid levels, nor that vegetarianism alters the effects of PGS on lipid levels. Conclusions: Vegetarianism is associated with reduced TC, LDL cholesterol, and HDL cholesterol, as well as elevated TG among EUR participants, with similar patterns for HDL cholesterol and TG in CSA participants. These association effects of vegetarianism on circulating lipids are similar across individuals with varying genetic capacity for lipid metabolism.