ImportanceThe epidemiological link between immune-mediated diseases (IMIDs) and cardiovascular disease has often been attributed to systemic inflammation. However, the direction of causality and the biological mechanisms linking cardiovascular disease with IMIDs are incompletely understood. Given the robust epidemiological association and the growing body of supportive mechanistic evidence, psoriasis is an exemplary IMID model for exploring this relationship.ObjectiveTo assess the bidirectional relationships between genetic predictors of psoriasis and the 2 major forms of cardiovascular disease, coronary artery disease (CAD) and stroke, and to evaluate the association between genetic predictors of cardiovascular disease with 9 other IMIDs.Design, Setting, and ParticipantsThis was a genetic association study using mendelian randomization (MR), a powerful genetic tool to help distinguish causation from associations observed in epidemiological studies, to provide supportive evidence for causality between traits. The study conducted 2-sample MR analyses using summary-level data from large-scale genome-wide association meta-analysis studies (GWAS) for each trait. The analysis focused on individuals of European descent from GWAS meta-analyses, involving CAD, stroke, psoriasis, and 9 other IMIDs. Data were analyzed from January 2023 to May 2024.ExposuresGenetic predictors of CAD, stroke, psoriasis, and 9 other IMIDs.Main Outcomes and MeasuresThe primary outcomes were the associations of genetic predictors of CAD and stroke with the risk of psoriasis and 9 other IMIDs, determined using inverse-variance weighted (IVW) MR estimates.ResultsThis study included 181 249 cases and 1 165 690 controls with CAD, 110 182 cases and 1 503 898 controls with stroke, 36 466 cases and 458 078 controls with psoriasis, for a total of approximately 3 400 000 individuals, and 9 other IMIDs. In contrast to previous assumptions, genetic predictors of psoriasis were found to have no association with CAD or stroke. In the reverse direction, genetic predictors of both CAD (MR estimate IVW odds ratio [OR], 1.07; 95% CI, 1.04-1.10; P = .003) and stroke (IVW OR, 1.22; 95% CI, 1.05-1.41; P = .01) were found to have risk-increasing associations with psoriasis. Adjusting for stroke rendered the associations of genetically predicted CAD with psoriasis risk nonsignificant (and vice versa), suggesting that a shared effect underlying genetic risk for CAD and stroke associates with increased psoriasis risk. No risk-increasing associations were observed for genetic predictors of cardiovascular disease with other common IMIDs, including rheumatoid arthritis and inflammatory bowel disease.Conclusions and RelevanceFindings of this mendelian randomization study indicate that genetic predictors of cardiovascular disease were associated with increased psoriasis risk with no reciprocal effect or association with other IMIDs. Elucidating mechanisms underpinning this association could lead to novel therapeutic approaches in both diseases.

中文翻译：

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探索心血管疾病遗传预测因子与银屑病之间的联系


重要性免疫介导疾病 （IMIDs） 与心血管疾病之间的流行病学联系通常归因于全身炎症。然而，因果关系的方向以及将心血管疾病与 IMID 联系起来的生物学机制尚不完全清楚。鉴于强大的流行病学关联和越来越多的支持机制证据，银屑病是探索这种关系的典型 IMID 模型。目的评估银屑病遗传预测因子与冠状动脉疾病 （CAD） 和中风 2 种主要形式的心血管疾病之间的双向关系，并评估心血管疾病遗传预测因子与其他 9 个 IMIDs.Design、环境和参与者之间的关联这是一项使用孟德尔随机化 （MR） 的遗传关联研究，孟德尔随机化是一种强大的遗传工具，可帮助区分因果关系与流行病学研究中观察到的关联， 为性状之间的因果关系提供支持证据。该研究使用来自大规模全基因组关联荟萃分析研究 （GWAS） 的摘要级数据对每个性状进行了 2 样本 MR 分析。该分析侧重于 GWAS 荟萃分析中的欧洲血统个体，涉及 CAD、中风、银屑病和其他 9 种 IMID。分析了 2023 年 1 月至 2024 年 5 月的数据。暴露 CAD、中风、银屑病和其他 9 种 IMID 的遗传预测因子主要结果和措施主要结果是 CAD 和中风的遗传预测因子与银屑病和其他 9 种 IMID 风险的关联，使用逆方差加权 （IVW） MR 估计确定。结果本研究包括 181 249 例 CAD 和 1 165 690 例对照，110 182 例和 1 503 898 例中风对照，36 466 例和 458 078 例银屑病对照，共约 3 400 000 例，以及 9 例其他 IMID。与以前的假设相反，发现银屑病的遗传预测因子与 CAD 或中风无关。相反，CAD 的遗传预测因子 （MR 估计 IVW 比值比 [OR]，1.07;95% CI，1.04-1.10;P = .003） 和中风 （IVW OR， 1.22;95% CI， 1.05-1.41;P = .01） 被发现与银屑病的风险增加相关。调整中风使遗传预测的 CAD 与银屑病风险的关联不显著（反之亦然），这表明 CAD 和中风遗传风险的共同效应与银屑病风险增加相关。未观察到心血管疾病的遗传预测因子与其他常见 IMIDs（包括类风湿性关节炎和炎症性肠病）的风险增加关联。结论和相关性这项孟德尔随机化研究的结果表明，心血管疾病的遗传预测因子与银屑病风险增加相关，与其他 IMID 没有互惠效应或关联。阐明支持这种关联的机制可能会导致这两种疾病的新型治疗方法。