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A bidirectional two-sample Mendelian randomization study to evaluate the relationship between psoriasis and
Lixia Yue1, Yihe Yan2, Shushan Zhao3
1Department of Rheumatology, Shaoxing People's Hospital, Shaoxing, Zhejiang, 312000, China. yuelixia_1988@sina.cn.
Background:
Prior observational studies have suggested a potential direct link between psoriasis (PSO) and interstitial lung disease (ILD). Consequently, we applied Mendelian randomization (MR) to further evaluate the bidirectional causal relationships between PSO and its different phenotypes [psoriatic arthritis (PSA)/psoriasis vulgaris (PSV)] and ILD.
Methods:
Data regarding PSO/PSA/PSV and ILD were sourced from publicly accessible genome-wide association studies (GWAS) databases, focusing on European populations. We used five algorithms- MR Egger, weighted median, inverse-variance weighted (IVW), simple mode, and weighted mode- to evaluate the causal relationships between PSO/PSA/PSV and ILD, with a primary emphasis on the IVW method.
Results:
The analysis indicated a potential association between PSA and an elevated risk of ILD [IVW odds ratio (OR): 1.035 (95% CI 1.008, 1.064; P = 0.012)], with no evidence of a direct relationship between total PSO and PSV with ILD. Conversely, no substantial evidence emerged from the reverse MR analysis to suggest that ILD significantly affects total PSO or the specific PSA/PSV phenotypes.
Conclusion:
Our findings provide genetic evidence supporting the notion that PSA may be a contributory risk factor for ILD. Further investigations are warranted to explore the underlying mechanisms of this potential causal relationship between PSA and ILD.
Insights
Psoriatic arthritis (PSA) may increase the risk of interstitial lung disease (ILD). This genetic study found no evidence that ILD causes psoriasis or its subtypes. Further research is needed to understand this link.
Area of Science:
- Rheumatology
- Pulmonology
- Genetics
Background:
- Observational studies suggest a link between psoriasis (PSO) and interstitial lung disease (ILD).
- The specific relationship between PSO subtypes and ILD requires further investigation.
- Genetic evidence can help clarify bidirectional causal relationships.
Purpose of the Study:
- To investigate the potential bidirectional causal relationship between psoriasis (and its subtypes, psoriatic arthritis [PSA] and psoriasis vulgaris [PSV]) and interstitial lung disease (ILD) using Mendelian randomization.
- To determine if PSA or PSV causally influence the risk of developing ILD.
- To assess if ILD causally influences the risk of developing PSO, PSA, or PSV.
Main Methods:
- Mendelian randomization (MR) analysis utilizing summary statistics from genome-wide association studies (GWAS) in European populations.
- Employed five MR algorithms: MR Egger, weighted median, inverse-variance weighted (IVW), simple mode, and weighted mode.
- Primary analysis focused on the IVW method to assess causal effects.
Main Results:
- A potential association was found between psoriatic arthritis (PSA) and an increased risk of interstitial lung disease (ILD) (IVW OR: 1.035, P=0.012).
- No significant causal relationship was detected between total psoriasis (PSO) or psoriasis vulgaris (PSV) and ILD.
- Reverse MR analysis showed no substantial evidence for ILD causally affecting PSO, PSA, or PSV.
Conclusions:
- Genetic evidence suggests psoriatic arthritis (PSA) may be a risk factor contributing to interstitial lung disease (ILD).
- The study did not find evidence for a causal link in the opposite direction, from ILD to PSO or its subtypes.
- Further research is recommended to elucidate the underlying biological mechanisms connecting PSA and ILD.
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