S76 Mendelian randomization study of cigarette smoking in idiopathic pulmonary fibrosis

Introduction and Objectives A cigarette smoking – idiopathic pulmonary fibrosis (IPF) association has been observed in several case-control studies. However, it is not known whether smoking causes IPF or if the observed association arises as a result of confounding (for example many studies have used population controls and may be vulnerable to selection bias). Mendelian randomization can offer an opportunity to investigate causality between cigarette smoking and IPF. Methods Genetic instruments for lifetime smoking score[1] (taking into account smoking duration and heaviness) were obtained from a genome-wide association study (GWAS) performed in UK Biobank (462,690 individuals, European ancestry). We used variants that were significantly associated with smoking at p Results 118 variants were used as instruments. In the main analysis, the odds ratio per standard deviation increase in lifetime smoking score was 0.6 (95%CI 0.4–1, p=0.07). Similar results were obtained in statistical sensitivity analyses. Conclusions This Mendelian randomization analysis does not provide evidence to support the notion that smoking causes IPF. It may be that confounding is responsible for the association in observational studies. Clearly, there is a strong case for stopping smoking for other reasons. References Wootton RE, Richmond RC, Stuijfzand BG, Lawn RB, Sallis HM, Taylor GM, Hemani G, Jones HJ, Zammit S, Smith GD, Munafo MR. Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study. Psychological Medicine 2019 Nov 6:1–9. Allen RJ, Guillen-Guio B, Oldham JM, Ma SF, Dressen A, Paynton ML, Kraven LM, Obeidat ME, Li X, Ng M, Braybrooke R. Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine 2020 Mar 1;201(5):564–74.