To the Editor: We read with interest the study “Psoriasis and COVID-19: A bidirectional Mendelian randomization study” by Chalitsios et al.1 Their results did not support the genetic association of psoriasis with COVID-19 that was reported by our study.2
The discrepancy between our findings and the current study can be explained by the differences with respect to the diagnostic method, study populations, and sample size. Compared with self-reported psoriasis in UK biobank, Chalitsios et al1 stated that they included 13,229 doctor-diagnosed psoriasis cases and elaborated a larger sample size to increase the power of test. Besides, the severity of COVID-19 was additionally evaluated in their study. The methodologies and data used by Chalitsios et al1 showed some advantages. However, 2 Genome-wide association studies6, 7 included in the original study did not mention that psoriasis was diagnosed by the dermatologist (about 4094 psoriasis cases).5 And the samples from Tsoi et al6 overlapped with datasets of Strange et al.4 Therefore, the classification of psoriasis was in fact heterogeneous in their study. In addition, sensitivity analysis is required for MR to assess the robustness of the results.7 In the study by Chalitsios et al1, they did not report the results of sensitivity analysis such as leave-one-out analysis. Last, the severity of a disease is generally used to evaluate the dose-response relationship. The authors did not evaluate whether psoriasis susceptibility was associated with the severity of COVID-19 by comparing mild, moderate, and severe cases.
The limitations of Mendelian randomization (MR) are noteworthy. Constructing a valid instrument variable is challenging, the power of test in MR is low because genetic variance only explains a small proportion of the exposure. The Beavis effect may exist in the results of MR because the associations can be biased by unmeasured confounders. Additionally, MR is a simulation of randomized controlled trials; however, the results of MR are confined to assumptions rather than real-world observations. The inconsistencies between MR and observational studies are commonly observed. Therefore, the association of psoriasis with the risk of COVID-19 warrants further evaluation in large-scale epidemiologic studies.
Conflicts of interest
None disclosed.
Acknowledgments
The authors would like to thank all the funders.
Footnotes
Funding sources: This work was supported by the National Key Research and Development Project of China “Precision Medicine Initiative” (2016YFC0900802) and the Program of Introducing Talents of Discipline to Universities (111 Project, No. B20017). The funders did not participate in this study.
IRB approval status: Not applicable.
Reprints not available from the authors.
References
- 1.Chalitsios C.V., Tsilidis K.K., Tzoulaki I. Psoriasis and COVID-19: a bidirectional Mendelian randomization study. J Am Acad Dermatol. 2022 doi: 10.1016/j.jaad.2022.10.019. [Epub ahead of print]. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Gu X., Chen X., Shen M. Association of psoriasis with risk of COVID-19: a 2-sample Mendelian randomization study. J Am Acad Dermatol. 2022;87(3):715–717. doi: 10.1016/j.jaad.2022.01.048. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Nair R.P., Duffin K.C., Helms C., et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009;41(2):199–204. doi: 10.1038/ng.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Strange A., Capon F., Spencer C.C., et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet. 2010;42(11):985–990. doi: 10.1038/ng.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Tsoi L.C., Stuart P.E., Tian C., et al. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nat Commun. 2017;8:15382. doi: 10.1038/ncomms15382. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Tsoi L.C., Spain S.L., Knight J., et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet. 2012;44(12):1341–1348. doi: 10.1038/ng.2467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Skrivankova V.W., Richmond R.C., Woolf B.A.R., et al. Strengthening the reporting of observational studies in Epidemiology using Mendelian randomization: the STROBE-MR statement. JAMA. 2021;326(16):1614–1621. doi: 10.1001/jama.2021.18236. [DOI] [PubMed] [Google Scholar]