Pos0943 a Genetic Study About Potential Causal Relationship Between Sedentary Activity and Psoriasis

Abstract

BackgroundPsoriasis is a common, chronic, immune-mediated skin disorder, which is characterized by clearly demarcated areas of erythematous plaques with overlying silvery scales appearing on the skin [1]. Previous studies have shown that plenty of psoriasis patients are engaged in less physical activity (PA), however, the genetic causal association between PA and psoriasis is of scarce evidence [2].ObjectivesIn this study, we aimed to evaluate the causal association between PA and psoriasis.MethodsWe used genome-wide association study (GWAS) data to conduct a Two-Sample Mendelian randomization (MR). MR utilizes single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to examine the causality of an observed association between exposure and outcome [3]. SNPs that were independent (r2 < 0.001) and without linkage disequilibrium and strongly related to PA (p < 1e-08, F>10), were selected as IVs. PA was divided into two parts including sedentary and physically active activities. Physically active behaviors include accelerometer-based physical activity, vigorous physical activity, moderate to vigorous physical activity, moderate physical activity 10+ minutes, and vigorous physical activity 10+ minutes. GWAS summary data of four types of sedentary behavior and five types of physically active behaviors were acquired from the UK biobank. The GWAS data of sedentary behavior includes watching TV (N=437,88), using computer(N=360,895), mobile phone use (N=310,555), and driving(N=456,972). The FinnGen collaboration provides summary statistics for psoriasis, which included 216,752 European individuals (4,510 cases and 212,242 non-cases). Inverse-variance weighted (IVW), MR-Egger, and the weighted median were used to assess causality. IVW was a key method to estimate. Cochran’s Q test and egger-intercept analysis were used as auxiliary analyses to assess pleiotropy and heterogeneity.ResultsThere were strong genetic causal relationships between psoriasis and TV watching. Watching TV was identified as the risk factor of psoriasis by IVW (OR =2.11; 95% Cl, 1.35-3.30, P=1.02E-03), identical to MR-Egger and the weighted median analysis. Pleiotropy and heterogeneity were not found by Cochran’s Q (P =0.140)and egger-intercept (P=0.43), suggesting these findings were reliable. In contrast, there was no causal relationship between the other activities and psoriasis (P > 0.05).Figure 1.Mendelian randomization results for gene-level causality between physical activity (PA) and psoriasis were evaluated by the odds ratio (OR) values of IVW, MR Egger, and Weighted median. Scatter plots (A), funnel plots (B), leave-one-out analysis (C), and forest plot (D) present TV watching as a risk factor for psoriasis. IVW, inverse-variance weighted; CI, confidence interval; SNP, single nucleotide polymorphisms.ConclusionOur findings reveal that TV watching is an apparent risk factor for psoriasis. It provides psoriasis patients with a piece of advice that they should lessen extended sedentary time and boost physical activity.References[1]Gr Greb, J. E., Goldminz, A. M., Elder, J. T., Lebwohl, M. G., Gladman, D. D., Wu, J. J., Mehta, N. N., Finlay, A. Y., & Gottlieb, A. B. (2016). Psoriasis. Nature reviews. Disease primers, 2, 16082.https://doi.org/10.1038/nrdp.2016.82[2]Wilson, P. B., Bohjanen, K. A., Ingraham, S. J., & Leon, A. S. (2012). Psoriasis and physical activity: a review. Journal of the European Academy of Dermatology and Venereology: JEADV, 26(11), 1345–1353.https://doi.org/10.1111/j.1468-3083.2012.04494.x[3]Davey Smith, G., & Hemani, G. (2014). Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Human molecular genetics, 23(R1), R89–R98.https://doi.org/10.1093/hmg/ddu328Acknowledgements:NIL.Disclosure of InterestsNone Declared.