Skip to main content
NCBI home page
Oxford University Press logoLink to Oxford University Press
. 2023 Mar 11;48(6):642–647. doi: 10.1093/ced/llad095

Relationship between genetically proxied vitamin D and psoriasis risk: a Mendelian randomization study

Patricia Bohmann 1,✉, Michael J Stein 2, Julian Konzok 3, Lam C Tsoi 4,5,6, James T Elder 7,8, Michael F Leitzmann 9, Sebastian-Edgar Baumeister 10, Hansjörg Baurecht 11,b,c
PMCID: PMC10259657  PMID: 36899474

Abstract

Background

Observational research suggests that vitamin D levels affect psoriasis. However, observational studies are prone to potential confounding or reverse causation, which complicates interpreting the data and drawing causal conclusions.

Aim

To apply Mendelian randomization (MR) methods to comprehensively assess a potential association between vitamin D and psoriasis.

Methods

Genetic variants strongly associated with 25-hydroxyvitamin D (25OHD) in genome-wide association study (GWAS) data from 417 580 and 79 366 individuals from two independent studies served as instrumental variables (used as the discovery and replication datasets, respectively). As the outcome variable, we used GWAS data of psoriasis (13 229 people in the case group, 21 543 in the control group). We used (i) biologically validated genetic instruments, and (ii) polygenic genetic instruments to assess the relationship between genetically proxied vitamin D and psoriasis. We carried out inverse-variance weighted (IVW) MR analyses for the primary analysis. In sensitivity analyses, we used robust MR approaches.

Results

MR analyses of both the discovery and replication datasets did not show an effect of 25OHD on psoriasis. Neither the IVW MR analysis of the biologically validated instruments [discovery dataset: odds ratio (OR) 0.99; 95% confidence interval (CI) 0.88–1.12, P = 0.873; replication dataset: OR 0.98, 95% CI 0.66–1.46, P = 0.930] nor that of the polygenic genetic instruments (discovery dataset: OR 1.00, 95% CI 0.81–1.22, P = 0.973; replication dataset: OR 0.94, 95% CI 0.64–1.38, P = 0.737) revealed an impact of 25OHD on psoriasis.

Conclusion

The present MR study did not support the hypothesis that vitamin D levels, measured by 25OHD, affect psoriasis. This study was conducted on Europeans, so the conclusions may not be applicable to all ethnicities.

Observational research suggests that vitamin D levels affect psoriasis; however, these studies are often subject to confounding and reverse causation. To investigate this potential causal relation, we carried out Mendelian randomization in two different ways by using (i) biologically validated genetic instruments, and (ii) genome-wide significant polygenic genetic instruments. In summary, results from both approaches did not indicate that vitamin D has a causal impact on psoriasis risk.

What is already known about this topic?

  • Previous observational research suggests a relationship between vitamin D and psoriasis.

  • Risk estimates from observational studies on the association of vitamin D and psoriasis are subject to potential confounding or reverse causation.

What does this study add?

  • Application of complementary Mendelian randomization approaches to investigate causality did not indicate an effect of vitamin D on psoriasis risk.

  • Use of biologically validated (i.e. variants in four gene regions related to vitamin D synthesis and metabolism) and polygenic (i.e. variants associated with 25-hydroxyvitamin D on a genome-wide level) genetic instruments for vitamin D provided further clarification of the relationship between vitamin D and risk of psoriasis.

Introduction

Psoriasis is a chronic inflammatory skin disease that typically first manifests as systemic, well-demarcated, erythematous oval plaques with adherent silvery scales.1 The prevalence of psoriasis is about 2–3%,2 but it is speculated that it is underdiagnosed and therefore undertreated.3 With at least 100 million people affected by psoriasis worldwide, in 2014 the World Health Organization passed a resolution on psoriasis and declared it a serious noncommunicable disease.4 Psoriasis is equally prevalent in both sexes and can occur at any age.1 The aetiology of psoriasis is not fully understood but several factors such as autoimmunological, genetic, hormonal or psychosomatic issues are thought to contribute to the development of the disease.1 There are three different forms of psoriasis treatment: phototherapy, systemic therapy as well as topical therapy that includes vitamin D3 as a common ingredient.2,4

In general, vitamin D is an essential fat-soluble vitamin primarily produced when the skin is exposed to ultraviolet radiation. 25-hydroxyvitamin D (25OHD) can serve as an approximation to determine vitamin D status. The evidence for the link between adequate vitamin D intake and health seems beyond doubt, especially for calcium-dependent diseases such as osteoporosis. However, some studies show limited health benefits from supplementation,5 with a recent large study showing no benefit even for preventing bone fracture.6

A potential multifactorial involvement of vitamin D is assumed in psoriasis: vitamin D represents a key modulator of inflammation mechanisms, immune modulation, cutaneous barrier integrity and keratinocyte differentiation, all thought to play a role in psoriasis.2 Previous observational studies investigating the association between 25OHD levels and psoriasis provided inconsistent results with most of them showing lower levels in patients with psoriasis compared with the general population.7,8 Some investigations did not find significant differences in 25OHD levels.9,10 Other studies have suggested that vitamin D deficiency is associated with the risk of psoriasis11; however, a large prospective study could not replicate this finding.12 Calcipotriol, a vitamin D analogue, has shown effectiveness in treating psoriasis in multiple small-scale randomized controlled trials (RCTs), however, it was mainly used in combination with other treatments such as the corticosteroid betamethasone.13,14

A recent study combining a prospective cohort and a Mendelian randomization (MR) analysis found a significant but not entirely convincing causal link between vitamin D and psoriasis risk.15 The authors solely utilized genome-wide significant predictors of 25OHD, independent of biological validation. Moreover, complementary pleiotropy-robust methods did not support the significant association with attenuated effects towards 1.15 A recent critical appraisal compared the choice of variants as predictors of 25OHD for assessing the causal relationship with cardiovascular disease using MR and recommended the selection of genetic instruments based on biological linkage. They argue that instruments chosen only by association often exhibit pleiotropic effects with low-density lipoprotein-cholesterol.16 Therefore, strong evidence on causality investigated with MR is lacking.17

To investigate the causal relationship between vitamin D and psoriasis, we applied MR methods. This approach uses genetic variants as instrumental variables to assess causality and thereby overcomes the risk of unmeasured confounding.18 We carried out a two-sample MR analysis by exploiting summary statistics from genome-wide association studies (GWASs) to examine the association between genetically instrumented vitamin D levels and psoriasis risk.

Materials and methods

To assess whether genetically proxied vitamin D levels are associated with the risk of psoriasis we used genetic instruments from four gene regions (GC, DHCR7, CYP2R1, CYP24A1) that are biologically linked to vitamin D (henceforth referred to as ‘focused instruments’)19 and genome-wide significant associated genetic variants (henceforth referred to as ‘polygenic instruments’) from summary statistics from a large 25OHD GWAS in 417 580 Europeans20 with a single nucleotide polymorphism (SNP) heritability of 0.13 explaining 41% of the total genetic heritability, which we refer to as the discovery dataset.

For psoriasis, SNP outcome associations were derived from a GWAS consisting of 13 229 ‘cases’ and 21 543 ‘controls’21 with 63 loci explaining 28% of the total genetic heritability.

In an additional analysis for further validation, we used genome-wide significant SNPs from another 25OHD GWAS including 79 366 Europeans,22 which we refer to as the replication dataset (for further information see Table 1). In both exposure GWASs, we used SNPs at a significance threshold of P < 5 × 10–8 for 25OHD as instrumental variables. For all included GWASs, ethical approval was granted, and informed consent was obtained from all participants.

Table 1.

Description of used datasets for each phenotype

Phenotype and subcohort Sample size/cases (control) Female, % Population Author(s) (year)
25OHD 417 580 54.0 European Revez et al. (2020)20
25OHD 79 366 N/A European Jiang et al. (2018)22
Psoriasis White Tsoi et al. (2017)21
 Total 13 229 (21 543) N/A
 CASP GWAS 1352 (1389) 52.5
 Kiel GWAS 464 (1135) 49.9
 Genizon GWAS 761 (993) 55.8
 WTCCC2 GWAS 2178 (5175) N/A
 Exomechip 3863 (4028) N/A
 PAGE Immunochip 3181 (7406) N/A
 PsA GWAS 1430 (1417) 52.3
Open in a new tab

25OHD, 25-hydroxyvitamin D; GWAS, genome-wide association study; N/A, not available; PsA, psoriatic arthritis.

Statistical analyses

We calculated statistical power according to Brion et al.23 and carried out two-sample MR analysis by instrumental variable approaches. A genetic variant can be considered a valid instrument if it fulfils the following assumptions: (i) the variant is robustly associated with the exposure (relevance assumption); (ii) there are no common causes of both the variant instrumenting the exposure and the outcome of interest (exchangeability assumption); and (iii) the variant affects the outcome exclusively through the exposure (exclusion restriction assumption). Instrument strength is assessed by calculating the proportion of explained exposure variance and the F-statistic.24 Violations of the exchangeability and exclusion restriction assumptions may occur through horizontal pleiotropy, i.e. the genetic variant affects the outcome via pathways other than through the exposure24 and can lead to an invalid causal estimation.

For the main analysis, we considered only genetic instruments from four gene regions (GC, DHCR7, CYP2R1, CYP24A1) as previously described to be biologically linked to vitamin D transport, metabolism and synthesis19 and thereby further minimized possible bias because of horizontal pleiotropy16 (Table S1; see Supporting Information).

We calculated Wald ratios for each SNP by dividing the SNP–psoriasis association by the SNP–25OHD association. Standard errors of the Wald ratios were approximated by the delta method.25 A multiplicative random-effects inverse-variance weighted (IVW) model was conducted to combine Wald ratios. Heterogeneity was investigated by Q and I2 statistics. For further sensitivity analyses, we performed various pleiotropy-robust methods including weighted median, radial regression, and MR pleiotropy residual sum and outlier (MR-PRESSO).24 In addition, we applied leave-one-out analysis to assess whether the IVW estimation was driven by a single SNP. Further, the MR Egger intercept test was conducted to evaluate potential influences of directional pleiotropy.

In a complementary analysis, we also considered all genome-wide significant instruments from two large 25OHD GWASs (Table 1).

Statistical analysis was conducted using the packages MendelianRandomization (0.4.2), TwoSampleMR (0.5.5) and MR-PRESSO (1.0) in R, version 4.0.6 (http://www.r-project.org/). We followed the STROBE-MR statement for reporting the methods and results.26 The study was not preregistered.

Results

Primary analysis using focused instruments

At a significance level of α = 5%, we had a power > 88% to detect an expected causal odds ratio (OR) for psoriasis of ≤ 0.8 (Table S2; see Supporting Information).

In line with the recommendation to select biologically relevant genetic variants as instruments in MR analyses whenever possible,16 we based our analyses on the focused instruments described elsewhere.27 Thirteen (from the discovery dataset) and four (from the replication dataset) variants strongly associated with 25OHD levels from the four gene regions (GC, DHCR7, CYP2R1, CYP24A1) biologically linked to vitamin D synthesis and metabolism had a minimum F-statistic of 83.14 and 94.88, respectively, and explained 5.2% and 2.6% of the phenotypic variability, respectively (Table S3; see Supporting Information).

We found no evidence for a causal association between genetically proxied 25OHD by biologically linked variants and the risk for psoriasis [discovery dataset: IVW OR 0.99, 95% confidence interval (CI) 0.88–1.12; P = 0.873; replication dataset: IVW OR 0.98; 95% CI 0.66–1.46, P = 0.930]. Pleiotropy-robust methods such as weighted median, IVW radial regression and MR-PRESSO confirmed the null association (Figure 1; Tables S3–S5, see Supporting Information).

Figure 1.

Figure 1

Open in a new tab

Mendelian randomization estimates for the relationship between genetically instrumented 25-hydroxyvitamin D and psoriasis. (a) Discovery dataset: Revez et al.;20 (b) replication dataset: Jiang et al.22 IVW, inverse variance weighted; MR-PRESSO, Mendelian randomization Pleiotropy RESidual Sum and Outlier; SNP, single nucleotide polymorphism.

Complementary analysis using polygenic instruments

At a significance level of α = 5%, we had a power > 89% to detect an expected causal OR for psoriasis of ≤ 0.8 (Table S2; see Supporting Information).

The 111 and 6 genetic instruments of the discovery and the replication GWAS datasets for the polygenic instrument analyses had a minimum F-statistic of 30.1 and 33.6, respectively, and explained 3.4% and 2.7% of the phenotypic variability, respectively (Table S3; see Supporting Information). Corroborating the findings of the primary analyses, we did not find any evidence for a causal association between genetically proxied 25OHD and the risk of psoriasis (discovery dataset: IVW OR 1.00, 95% CI 0.81–1.22, P = 0.973; replication dataset: IVW OR = 0.94, 95% CI = 0.64–1.38; P = 0.737).

Similar to IVW, all pleiotropy-robust methods confirmed the null findings (Figure 1). We found moderate heterogeneity in the IVW analysis, but no evidence for directional pleiotropy (Table S4; see Supporting Information). The leave-one-out analysis did not indicate any single SNP estimate as a leverage point with high impact on the overall causal estimate (Table S5; see Supporting Information).

Discussion

The findings of the present MR study do not support a causal link between genetically determined 25OHD levels and the risk of psoriasis, neither using focused instruments nor polygenic instruments. We had sufficient power to detect moderate effects and the results yielded consistent OR estimates close to 1 using different MR approaches and sensitivity analyses.

As small-scale RCTs have found a beneficial effect of the vitamin D derivative calcipotriol in the treatment of psoriasis,13,14,28,29 and because several observational studies found a role for vitamin D in the pathogenesis of psoriasis,4,30–33 a causal link between vitamin D and psoriasis seems apparent but causality has not yet been proven. In addition, the effectiveness of vitamin D supplementation for people with psoriasis remains controversial.31–33 One possible explanation for contradictory results could be dose-dependent effects of vitamin D in psoriasis.34 In addition, observational studies are prone to confounder bias, which may explain discrepancies between study results. Certain potential confounders have already been proposed: diet,35 obesity,36 ultraviolet exposure, skin types, smoking status, season and methodological differences in measuring vitamin D levels.17

Despite the methodological issues of observational studies, the relationship between vitamin D and psoriasis is the subject of many studies and is also of great importance with regard to comorbidities such as obesity or diabetes.37 Causal inference using MR, which is less susceptible to unmeasured confounding and reverse causation, could shed light on this issue and help draw clear conclusions. With 41% of the total genetic heritability for vitamin D and 28% of the total genetic heritability in psoriasis, SNP heritabilities in the current study indicate a moderate-to-high additive genetic effect of the used SNPs compared with other diseases,38 supporting the validity of our results.

Our results are inconsistent with a recently published study combining evidence from a prospective cohort and an MR analysis.15 The authors suggested a causal inverse relationship between genetically determined 25OHD and risk of psoriasis.15 Yet, those findings are not entirely convincing. First, although Zhang et al.15 applied two-sample MR methods, the data sources for the exposure (25OHD levels) and the outcome (psoriasis: MRC-IEU) were obtained from the same database (UK Biobank) and were thus not independent, violating the two-sample MR key assumption.24 Second, the MR results reported by Zhang et al.15 were ambiguous, as the pleiotropy-robust methods did not show significant results and ORs were attenuated towards 1. Third, the authors used solely the genome-wide significance criterion for instrument selection regardless of their biological relevance as recommended previously.16 Finally, psoriasis ascertainment in the MRC-IEU was based on self-report, whereas our exposure GWAS consisted of dermatologist-diagnosed cases of people with psoriasis.21

Our study has several limitations. The analysis assumes a linear relationship between 25OHD levels and the log-transformed OR of psoriasis risk. Risk estimates may be misleading if the true relationship is nonlinear. However, they still reflect presence and direction of the causal effect.39 A protective effect may occur only in certain subgroups, but we lacked access to individual-level data to investigate effect modification and subgroup identifications.40 MR results may also be biased if genetic instruments of 25OHD change over time, as the importance of sun exposure and vitamin D for certain diseases may be limited to early life.41 In that case, an MR study using genetic instruments associated with circulating 25OHD levels after a critical timeframe would fail to detect a significant association. One way to minimize that potential bias is to use an average across multiple variant effects (as carried out in the current study using multiplicative random effects IVW).41

Our study exploits genetic instruments exclusively from European ancestry studies (exposure and outcome GWASs), which minimizes the risk of population stratification bias and increases the plausibility of the two-sample MR assumption. Nevertheless, caution should be exercised before generalizing results to other ethnicities. Further, restricting the analyses to only biologically relevant genetic instruments using focused instruments follows a recent recommendation16 and strengthens our findings.

In conclusion, our study does not indicate that genetically proxied 25OHD causally affects psoriasis. Our findings suggest that associations identified in previous, mainly observational, studies may have been subject to environmental confounding or reverse causation. MR studies are valuable as an alternative line of aetiological evidence that complements traditional RCT-based causal inference. To provide more definitive evidence against a causal role of 25OHD in psoriasis risk, long-term RCT studies would be needed.

Supplementary Material

llad095_Supplementary_Data
Click here for additional data file. (86.3KB, docx)

Acknowledgments

The authors thank the investigators of the original GWAS studies for sharing summary data used in this study.

Contributor Information

Patricia Bohmann, Department of Epidemiology and Preventive Medicine, University of Regensburg, Germany.

Michael J Stein, Department of Epidemiology and Preventive Medicine, University of Regensburg, Germany.

Julian Konzok, Department of Epidemiology and Preventive Medicine, University of Regensburg, Germany.

Lam C Tsoi, Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics and; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

James T Elder, Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI, USA.

Michael F Leitzmann, Department of Epidemiology and Preventive Medicine, University of Regensburg, Germany.

Sebastian-Edgar Baumeister, Institute of Health Services Research in Dentistry, University of Münster, Münster, Germany.

Hansjörg Baurecht, Department of Epidemiology and Preventive Medicine, University of Regensburg, Germany.

Funding sources

L.C.T. and J.T.E. are supported by awards from the National Institutes of Health (K01AR072129 to L.C.T.; P30AR075043 to L.C.T. and J.T.E.; R01AR042742, R01AR050511, R01AR054966, R01AR063611 and R01AR065183 to J.T.E.) and the Babcock Memorial Trust. J.T.E. is supported by the Ann Arbor VA Hospital. L.C.T. has received support from Janssen, and Galderma.

Data availability

The GWAS summary statistics for psoriasis without the 23andMe component can be made available on request to the author. The vitamin D summary statistics are available at: https://cnsgenomics.com/content/data. Code availability: the analysis code in R is available on request to the author.

Ethics statement

Ethical approval: Ethical approval was granted for each of the cohorts. Informed consent: all patients gave written, informed consent for participation and publication of their case details and images.

Supporting Information

Additional Supporting Information may be found in the online version of this article at the publisher’s website.

References

  • 1. Boehncke WH, Schön MP. Psoriasis. Lancet 2015; 386:983–94. [DOI] [PubMed] [Google Scholar]
  • 2. Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA 2020; 323:1945–60. [DOI] [PubMed] [Google Scholar]
  • 3. Kim WB, Jerome D, Yeung J. Diagnosis and management of psoriasis. Can Fam Physician 2017; 63:278–85. [PMC free article] [PubMed] [Google Scholar]
  • 4. World Health Organization . Global Report on Psoriasis. Geneva: WHO, 2016. [Google Scholar]
  • 5. Bouillon R, Manousaki D, Rosen C. et al. The health effects of vitamin D supplementation: evidence from human studies. Nat Rev Endocrinol 2022; 18:96–110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. LeBoff MS, Chou SH, Ratliff KA. et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med 2022; 387:299–309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Chandrashekar L, Kumarit GR, Rajappa M. et al. 25-hydroxy vitamin D and ischaemia-modified albumin levels in psoriasis and their association with disease severity. Br J Biomed Sci 2015; 72:56–60. [DOI] [PubMed] [Google Scholar]
  • 8. Gisondi P, Rossini M, Di Cesare A. et al. Vitamin D status in patients with chronic plaque psoriasis. Br J Dermatol 2012; 166:505–10. [DOI] [PubMed] [Google Scholar]
  • 9. Solak B, Dikicier BS, Celik HDet al. Bone mineral density, 25-OH vitamin D and inflammation in patients with psoriasis. Photodermatol Photoimmunol Photomed 2016; 32:153–60. [DOI] [PubMed] [Google Scholar]
  • 10. Wilson PB. Serum 25-hydroxyvitamin D status in individuals with psoriasis in the general population. Endocrine 2013; 44:537–9. [DOI] [PubMed] [Google Scholar]
  • 11. Umar M, Sastry KS, Al Ali F. et al. Vitamin D and the pathophysiology of inflammatory skin diseases. Skin Pharmacol Physiol 2018; 31:74–86. [DOI] [PubMed] [Google Scholar]
  • 12. Merola JF, Han J, Li T. et al. No association between vitamin D intake and incident psoriasis among US women. Arch Dermatol Res 2014; 306:305–7. [DOI] [PubMed] [Google Scholar]
  • 13. Heim M, Irondelle M, Duteil L. et al. Impact of topical emollient, steroids alone or combined with calcipotriol, on the immune infiltrate and clinical outcome in psoriasis. Exp Dermatol 2022; 31:1764–78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Yelamos O, Alejo B, Ertekin SS. et al. Non-invasive clinical and microscopic evaluation of the response to treatment with clobetasol cream vs. calcipotriol/betamethasone dipropionate foam in mild to moderate plaque psoriasis: an investigator-initiated, phase IV, unicentric, open, randomized clinical trial. J Eur Acad Dermatol Venereol 2021; 35:143–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Zhang Y, Jing D, Zhou G. et al. Evidence of a causal relationship between vitamin D status and risk of psoriasis from the UK Biobank Study. Front Nutr 2022; 9:807344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Burgess S, Gill D. Genetic evidence for vitamin D and cardiovascular disease: choice of variants is critical. Eur Heart J 2022; 43:1740–2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Hambly R, Kirby B. The relevance of serum vitamin D in psoriasis: a review. Arch Dermatol Res 2017; 309:499–517. [DOI] [PubMed] [Google Scholar]
  • 18. Smith G Davey, Holmes MV, Davies NM. et al. Mendel's laws, Mendelian randomization and causal inference in observational data: substantive and nomenclatural issues. Eur J Epidemiol 2020; 35:99–111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Wang TJ, Zhang F, Richards JB. et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 2010; 376:180–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Revez JA, Lin T, Qiao Z. et al. Genome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration. Nat Commun 2020; 11:1647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Tsoi LC, Stuart PE, Tian C. et al. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nat Commun 2017; 8:15382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Jiang X, O'Reilly PF, Aschard H. et al. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nat Commun 2018; 9:260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Brion MJ, Shakhbazov K, Visscher PM. Calculating statistical power in Mendelian randomization studies. Int J Epidemiol 2013; 42:1497–501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Burgess S, Davey Smith G, Davies NM. et al. Guidelines for performing Mendelian randomization investigations. Wellcome Open Res 2019; 4:186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for Mendelian randomization. Stat Methods Med Res 2017; 26:2333–55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Skrivankova VW, Richmond RC, Woolf BAR. et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration. BMJ 2021; 375:n2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Emerging Risk Factors Collaboration E-CVDVDSC . Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses. Lancet Diabetes Endocrinol 2021; 9:837–46. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  • 28. de Rie MA, de Hoop D, Jonsson L. et al. Pharmacoeconomic evaluation of calcipotriol (Daivonex/Dovonex) and UVB phototherapy in the treatment of psoriasis: a Markov model for The Netherlands. Dermatology 2001; 202:38–43. [DOI] [PubMed] [Google Scholar]
  • 29. Lebwohl M, Kircik L, Lacour JP. et al. Twice-weekly topical calcipotriene/betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (PSO-LONG trial). J Am Acad Dermatol 2021; 84:1269–77. [DOI] [PubMed] [Google Scholar]
  • 30. Mattozzi C, Paolino G, Salvi M. et al. Peripheral blood regulatory T cell measurements correlate with serum vitamin D level in patients with psoriasis. Eur Rev Med Pharmacol Sci 2016; 20:1675–9. [PubMed] [Google Scholar]
  • 31. Wadhwa B, Relhan V, Goel K. et al. Vitamin D and skin diseases: a review. Indian J Dermatol Venereol Leprol 2015; 81:344–55. [DOI] [PubMed] [Google Scholar]
  • 32. Soleymani T, Hung T, Soung J. The role of vitamin D in psoriasis: a review. Int J Dermatol 2015; 54:383–92. [DOI] [PubMed] [Google Scholar]
  • 33. Mattozzi C, Paolino G, Richetta AG. et al. Psoriasis, vitamin D and the importance of the cutaneous barrier's integrity: an update. J Dermatol 2016; 43:507–14. [DOI] [PubMed] [Google Scholar]
  • 34. Reichrath J. Vitamin D and the skin: an ancient friend, revisited. Exp Dermatol 2007; 16:618–25. [DOI] [PubMed] [Google Scholar]
  • 35. Barrea L, Macchia PE, Tarantino G. et al. Nutrition: a key environmental dietary factor in clinical severity and cardio-metabolic risk in psoriatic male patients evaluated by 7-day food-frequency questionnaire. J Transl Med 2015; 13:303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Savastano S, Barrea L, Savanelli MC. et al. Low vitamin D status and obesity: role of nutritionist. Rev Endocr Metab Disord 2017; 18:215–25. [DOI] [PubMed] [Google Scholar]
  • 37. Barrea L, Savanelli MC, Di Somma C. et al. Vitamin D and its role in psoriasis: an overview of the dermatologist and nutritionist. Rev Endocr Metab Disord 2017; 18:195–205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. So HC, Gui AH, Cherny SS. et al. Evaluating the heritability explained by known susceptibility variants: a survey of ten complex diseases. Genet Epidemiol 2011; 35:310–17. [DOI] [PubMed] [Google Scholar]
  • 39. Burgess S, Davies NM, Thompson SG. et al. Instrumental variable analysis with a nonlinear exposure-outcome relationship. Epidemiology 2014; 25:877–85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. Rees JMB, Foley CN, Burgess S. Factorial Mendelian randomization: using genetic variants to assess interactions. Int J Epidemiol 2020; 49:1147–58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Labrecque JA, Swanson SA. Interpretation and potential biases of Mendelian randomization estimates with time-varying exposures. Am J Epidemiol 2019; 188:231–8. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

llad095_Supplementary_Data
Click here for additional data file. (86.3KB, docx)

Data Availability Statement

The GWAS summary statistics for psoriasis without the 23andMe component can be made available on request to the author. The vitamin D summary statistics are available at: https://cnsgenomics.com/content/data. Code availability: the analysis code in R is available on request to the author.

Articles from Clinical and Experimental Dermatology are provided here courtesy of Oxford University Press

RESOURCES