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

<strong>Objectives</strong>: To determine the associations of vegetarianism with 30 serum biomarkers, and to identify genetic variants that modify these associations. <strong>Design</strong>: A population-based cohort study. <strong>Setting</strong>: United Kingdom. <strong>Participants</strong>: 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. <strong>Main outcome measures</strong>: Effects of vegetarianism and gene-vegetarianism interactions on 30 serum biomarkers for diabetes, cancer, cardiovascular, skeletal, renal, and liver diseases. <strong>Results</strong>: 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 (<em>P</em> 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 <em>MMAA</em>, 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, <em>RNF168</em> in testosterone (<em>P</em> = 1.45e-06) and <em>ZNF277</em> in eGFR (<em>P</em> = 6.76e-07), which have previously been associated with testicular and renal traits, respectively. <strong>Conclusions</strong>: 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.