The role of linoleic acid in asthma and inflammatory markers: a Mendelian randomization study

Background: Asthma is a common respiratory disease, possibly caused by autoimmunity. Linoleic acid (LA), the main n-6 (omega-6) PUFA from widely used vegetable oils, is thought to suppress immune responses that might have benefits for asthma. However, this question has not been examined in randomized controlled trials. Objectives: The aim of this study was to obtain unconfounded estimates, we assessed how genetically predicted LA affected asthma using 2-sample Mendelian randomization. We also examined its role in white blood cell traits (eosinophil, neutrophil, and low monocyte counts) identified as potential causal factors in asthma. Methods: We used 18 uncorrelated, genome-wide significant genetic variants to predict LA, which we applied to a large genetic case (n = 19,954)-control (n = 107,715) study of asthma, to the UK Biobank (408,961 people of European ancestry with 26,332 asthma cases), and for white blood cell traits to the UK Biobank. We also repeated the analysis on asthma using 29 replicated, functionally relevant genetic variants. In addition, we examined the role of asthma in LA to assess reverse causality. Results: Genetically predicted LA was associated with lower risk of asthma (OR: 0.89 per SD increase in LA; 95% CI: 0.85, 0.93), with no association of asthma with LA. Genetically predicted LA was associated with lower eosinophil count (-0.03; 95% CI: -0.061, -0.004) and lower neutrophil count (-0.04; 95% CI: -0.057, -0.023). These estimates were robust to different selections of genetic variants and sensitivity analyses. Conclusions: LA might protect against asthma possibly via white blood cell traits, with relevance to the identification of effective new interventions for asthma.