Gene-vegetarianism interactions in calcium, testosterone, and eGFR identified in genome-wide analysis across 30 biomarkers

Abstract

Large cohort studies showing health impacts of vegetarianism have not considered differences in genetics. We designed a rigorous definition of vegetarianism using data from two surveys in the UK Biobank to identify a reliable cohort of vegetarians. Vegetarians were matched 1:4 with non-vegetarians, revealing significant effects of vegetarianism in 15 of 30 serum biomarkers. Notably, all cholesterol measures plus Vitamin D (P= 2.1e-49) were significantly lower in vegetarians, while triglycerides were higher (P= 4.0e-26). We performed a genome-wide association study and found no significant associations with vegetarianism as a trait. Finally, we performed the first ever genome-wide gene-vegetarianism interaction analyses for 30 biomarker traits (N = 147,253). We detected evidence of gene-vegetarianism interaction with one genome-wide significant variant at rs72952628 (P= 4.47e-08), where the heterozygous genotype was associated with higher calcium in vegetarians. rs72952628 is located inMMAA, which is part of the B12metabolism pathway; B12has a high deficiency potential in vegetarians. Gene-based aggregation of interactionP-values revealed two additional significant genes,RNF168in testosterone (P= 1.45e-06), andDOCK4in eGFR (P= 6.76e-07), which have previously been associated with testicular and renal traits, respectively. These nutrigenetic findings suggest differences in genotype may play a role in moderating the benefits a vegetarian diet.