Alcohol Consumption and Smoking in Relation to Psoriasis

A Mendelian Randomization Study

Jiahe Wei; Jiahao Zhu; Huiqing Xu; Dan Zhou; James T. Elder; Lam C. Tsoi; Matthew T. Patrick; Yingjun Li

Disclosures

The British Journal of Dermatology. 2022;187(5):684-691. 

In This Article

Abstract and Introduction

Abstract

Background: Alcohol consumption and smoking have been reported to be associated with psoriasis risk. However, a conclusion with high-quality evidence of causality could not be easily drawn from regular observational studies.

Objectives: This study aims to assess the causal associations of alcohol consumption and smoking with psoriasis.

Methods: Genome-wide association study (GWAS) summary-level data for alcohol consumption (N = 941 280), smoking initiation (N = 1 232 091), cigarettes per day (N = 337 334) and smoking cessation (N = 547 219) was obtained from the GSCAN consortium (Sequencing Consortium of Alcohol and Nicotine use). The GWAS results for lifetime smoking (N = 462 690) were obtained from the UK Biobank samples. Summary statistics for psoriasis were obtained from a recent GWAS meta-analysis of eight cohorts comprising 19 032 cases and 286 769 controls and the FinnGen consortium, comprising 4510 cases and 212 242 controls. Linkage disequilibrium score regression was applied to compute the genetic correlation. Bidirectional Mendelian randomization (MR) analyses were conducted to determine casual direction using independent genetic variants that reached genome-wide significance (P < 5 × 10–8).

Results: There were genetic correlations between smoking and psoriasis. MR revealed a causal effect of smoking initiation [odds ratio (OR) 1·46, 95% confidence interval (CI) 1·32–1·60, P = 6·24E-14], cigarettes per day (OR 1·38, 95% CI 1·13–1·67, P = 0·001) and lifetime smoking (OR 1·96, 95% CI 1·41–2·73, P = 7·32E-05) on psoriasis. Additionally, a suggestive causal effect of smoking cessation on psoriasis was observed (OR 1·39, 95% CI 1·07–1·79, P = 0·012). We found no causal relationship between alcohol consumption and psoriasis (P = 0·379). The reverse associations were not statistically significant.

Conclusions: Our findings provide causal evidence for the effects of smoking on psoriasis risk.

Introduction

Psoriasis is a complex chronic immune-mediated inflammatory disease of the skin or joints affecting approximately 2% of the global population and is a leading cause of severe comorbidities.[1] Modifiable lifestyle factors, such as smoking and alcohol consumption, have been considered potential risk factors for psoriasis.[2,3] A prospective study showed that alcohol consumption could increase psoriasis risk.[4] However, another two recent cohort studies did not support a clear link between alcohol consumption and psoriasis.[5,6] Current evidence on the relationship between alcohol consumption and psoriasis is controversial. Although a positive association between smoking and psoriasis was well identified by observational studies,[2,7] these studies are susceptible to uncontrolled confounders.[5] For example, depression is a potential confounder because it increases the risk of both smoking and psoriasis.[8,9]

Considering the weakness of regular observational studies, whether the association between alcohol consumption as well as smoking and psoriasis reflects true causation or is confounded remains unclear. Mendelian randomization (MR) offers a means, utilizing genetic variants as instrumental variables (IVs), to infer the causal effect between the exposure and the outcome,[10] as genetic variation (1) is fixed and randomly assigned during meiosis, and (2) is not affected by environmental factors, which minimizes potential confounders and reverse causality.[11] Here, we implemented bidirectional MR analyses to explore the causal relationship between alcohol consumption as well as smoking and psoriasis.

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