Gene-vegetarianism interactions detected in genome-wide analyses across 30 serum biomarkers: a population-based cohort study in UK Biobank (Supplementary Tables)

Objectives: To determine the associations of vegetarianism with 30 serum biomarkers, and to identify genetic variants that modify these associations. Design: A population-based cohort study. Setting: United Kingdom. Participants: A total of 155,375 UK Biobank participants with biomarker measurements, genetic data, dietary information, and relevant covariates were included. A rigorous sample of vegetarians was defined based on consistent responses to four questions in two dietary surveys. Main outcome measures: Effects of vegetarianism and gene-vegetarianism interactions on 30 serum biomarkers for diabetes, cancer, cardiovascular, skeletal, renal, and liver diseases. Results: Compared to a matched sample of non-vegetarians, vegetarians had significantly lower levels of all cholesterol measures and vitamin D, and a higher level of triglycerides, while no significant differences were observed for sex hormones. We found a genetic variant, rs72952628 (C/T), that modified the association between vegetarianism and serum calcium (P for interaction = 4.47e-08). Vegetarianism was associated with a 0.13 units decrease (95% confidence interval -0.09 to -0.18) in calcium in CC individuals, but with 0.30 units increase (0.14 to 0.46) in CT individuals. This variant is located in the gene MMAA, which is part of the vitamin B12 metabolism pathway; B12 has a high nutrient deficiency potential in vegetarians. Gene-based interaction analysis revealed two additional significant genic regions, RNF168 in testosterone (P = 1.45e-06) and ZNF277 in eGFR (P = 6.76e-07), which have previously been associated with testicular and renal traits, respectively. Conclusions: Vegetarianism was associated with 15 of the 30 serum biomarkers examined, and evidence of genetic modifications was found for three biomarkers: calcium, testosterone, and eGFR.