Department of Epidemiology and Preventive Medicine, University of Regensburg, Germany.
Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
Clin Exp Dermatol. 2023 Jun 5;48(6):642-647. doi: 10.1093/ced/llad095.
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.
To apply Mendelian randomization (MR) methods to comprehensively assess a potential association between vitamin D and psoriasis.
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.
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.
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.
观察性研究表明，维生素 D 水平会影响银屑病。然而，观察性研究容易受到潜在混杂因素或反向因果关系的影响，这使得解释数据和得出因果结论变得复杂。
应用孟德尔随机化（MR）方法全面评估维生素 D 与银屑病之间的潜在关联。
来自两个独立研究的 417580 人和 79366 人的全基因组关联研究（GWAS）数据中与 25-羟维生素 D（25OHD）强烈相关的遗传变异作为工具变量（分别用作发现和复制数据集）。作为结局变量，我们使用了银屑病的 GWAS 数据（病例组 13229 人，对照组 21543 人）。我们使用了（i）经过生物学验证的遗传工具，以及（ii）多基因遗传工具来评估遗传上与维生素 D 相关的银屑病。我们进行了基于逆方差加权（IVW）的主要分析。在敏感性分析中，我们使用了稳健的 MR 方法。
对发现数据集和复制数据集的 MR 分析均未显示 25OHD 对银屑病的影响。基于生物学验证工具的 IVW MR 分析（发现数据集：比值比（OR）0.99；95%置信区间（CI）0.88-1.12，P=0.873；复制数据集：OR 0.98，95%CI 0.66-1.46，P=0.930）和多基因遗传工具的 IVW MR 分析（发现数据集：OR 1.00，95%CI 0.81-1.22，P=0.973；复制数据集：OR 0.94，95%CI 0.64-1.38，P=0.737）均未显示 25OHD 对银屑病的影响。
本 MR 研究不支持维生素 D 水平（通过 25OHD 测量）影响银屑病的假设。本研究是在欧洲人群中进行的，因此结论可能不适用于所有种族。
