Association of psoriasis with risk of COVID-19: A 2-sample Mendelian randomization study.

To the Editor:

With the growing pandemic of COVID-19, psoriasis has been reported to be linked with COVID-19 from genetic and epidemiological perspectives, especially in patients receiving systemic treatments.1, 2, 3 However, traditional epidemiology is inevitably affected by confounding bias. Mendelian randomization (MR) is an approach based on genome-wide association studies to construct instrumental variables (IVs) and can effectively control the confounding bias of observational studies. IVs refer to variables that only affect the outcome through risk factors, and MR uses single-nucleotide polymorphisms as IVs to identify risk factors. MR draws on the experiences of randomized trials and uses the Mendelian law of heredity that parental alleles are randomly assigned to the offspring to simulate the causal relationships between exposures and outcomes. Here, we performed a 2-sample MR, in which genetic associations with exposures and outcomes are estimated in different sets of individuals, to investigate the association of psoriasis with COVID-19.

We downloaded the summary data from open-access genome-wide association studies data sets at https://gwas.mrcieu.ac.uk/. We used R 4.0.4 and package “TwoSampleMR,” and statistical methods can be found in the guidelines (https://mrcieu.github.io/TwoSampleMR). We used the inverse variance weighted (IVW) method as the primary approach and other algorithms as the supplementary methods. We then tested pleiotropy using MR-Egger regression because valid MR estimations require IVs to be independent of outcomes. Finally, reverse MR and sensitivity analysis were used to test the unidirectionality and robustness of the results, respectively. A P value of <.05 was considered statistically significant.

For psoriasis, we extracted the results from the studies by the Neale laboratory, with 3871 cases and 333,288 controls, to generate the IVs (https://gwas.mrcieu.ac.uk/datasets/ukb-a-100/). For COVID-19, the data from the COVID-19 Host Genetics Initiative with 14,134 cases and 1,284,876 controls were gathered as the outcome variables (https://gwas.mrcieu.ac.uk/datasets/ebi-a-GCST010776/). After removing linkage disequilibrium, 28 single-nucleotide polymorphisms were selected from the exposure datasheet and incorporated into the outcome datasheet. The IVW method, in conjunction with other methods (Fig 1 ), suggested that the genetic risk of psoriasis was associated with increased susceptibility to COVID-19 (β IVW = 2.94, P = .01). The MR-Egger regression identified no significant horizontal pleiotropy (P = .74). The reverse MR analysis treating COVID-19 as the exposure and psoriasis as the outcome demonstrated an insignificant association (P = .94), indicating the unidirectionality of the relationship. The leave-one-out sensitivity analysis that removed 1 SNP at a time showed stable results, except for rs13196409 (Fig 2 ).

Fig 1

Two-sample MR analysis of the effect of psoriasis on COVID-19 using different methods. MR, Mendelian randomization; SNP, single-nucleotide polymorphism.

Fig 2

Leave-one-out sensitivity analysis of the effect of psoriasis on COVID-19.

Our study revealed a unidirectional effect of psoriasis on COVID-19. By constructing IVs, the associations estimated by the MR analysis have greater accuracy because these estimates are less confounded by socioeconomic, environmental, and behavioral factors, and the timing of causality is reasonable. The finding could be conducive to comprehending the underlying impacts of psoriasis on the phenotype of COVID-19. Previous studies have revealed that patients with psoriasis would probably have an increased risk of developing severe infections; this may be because of the use of immunosuppressants such as methotrexate. Future research could concentrate on assessing the effects of systemic drugs such as immunosuppressants on the association of psoriasis with COVID-19.

Conflicts of interest

None disclosed.