Relationship between genetically proxied vitamin D and psoriasis risk: a Mendelian randomization study.
Relationship between genetically proxied vitamin D and psoriasis risk: a Mendelian randomization study.
复制标题
遗传代理维生素 D 与牛皮癣风险之间的关系：孟德尔随机化研究。
DOI：
10.1093/ced/llad095
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发表时间：
2023
影响因子：
4.1
通讯作者：
Baurecht,Hansjörg
中科院分区：
文献类型：
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作者：
Bohmann,Patricia;Stein,MichaelJ;Konzok,Julian;Tsoi,LamC;Elder,JamesT;Leitzmann,MichaelF;Baumeister,Sebastian-Edgar;Baurecht,Hansjörg
背景观察性研究表明维生素D水平影响银屑病。然而，观察性研究容易出现潜在的混淆或反向因果关系，目的应用孟德尔随机化（Mendelian randomization，MR）方法对维生素D与银屑病之间的潜在关联进行综合评估。来自两项独立研究的417580和79366个人的数据用作工具变量（分别用作发现和复制数据集）。作为结果变量，我们使用银屑病的GWAS数据（病例组13 229人，对照组21 543人）。我们使用（i）生物学验证的遗传工具，和（ii）多基因遗传工具来评估遗传代理维生素D和银屑病之间的关系。我们对主要分析进行了逆方差加权（IVW）MR分析。在敏感性分析中，我们使用强大的MR approaches.ResultsMR分析的发现和复制数据集没有显示25 OHD对银屑病的影响。生物学验证仪器的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]和多基因遗传仪器的IVW MR分析均未显示（发现数据集：OR 1.00，95%CI 0.81- 1.22，P = 0.973;重复数据集：OR 0.94，95%CI 0.64- 1.38，P = 0.737）揭示了25 OHD对银屑病的影响。这项研究是在欧洲人中进行的，因此结论可能不适用于所有种族。
BackgroundObservational 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.AimTo apply Mendelian randomization (MR) methods to comprehensively assess a potential association between vitamin D and psoriasis.MethodsGenetic 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.ResultsMR 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.ConclusionThe 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.