Role of linoleic acid in autoimmune disorders: a Mendelian randomisation study

Autoimmune diseases are a major challenge for global health. From an evolutionary biology perspective, reproduction, particularly androgens, trades off against immune activity.1 Correspondingly, trials suggest androgens improve rheumatoid arthritis (RA).2 3 As such, dietary factors promoting reproduction might prevent or treat autoimmune disorders. Linoleic acid (LA) is a major n−6 polyunsaturated fatty acid (PUFA) in widely used polyunsaturated vegetable oils, such as sunflower, corn, soybean and cottonseed oil. In animal experiments, LA stimulates the synthesis of testosterone.4 Observationally, endogenous LA is inversely associated with RA5 and systemic lupus erythematosus (SLE),6 but these findings have not been confirmed in randomised controlled trials. Comparing autoimmune disorders according to naturally occurring LA-related genetic variants, that is, Mendelian randomisation (MR), provides a means of obtaining unconfounded estimates of causal effects. We obtained strong, independent genetic predictors of LA using (1) the three most significant uncorrelated single-nucleotide polymorphisms (SNPs) and (2) …