Association between uric acid and aortic aneurysms: A two-sample Mendelian randomization study

Based on Mendelian randomization (MR) methods, this study aims to explore causal associations of uric acid (UA) levels with aortic aneurysms (AAs). In this MR study, data on UA levels and gout were extracted from genome-wide association study (GWAS) meta-analysis conducted by UK Biobank (UKB) for European population and the Biobank Japan Project (BBJ) for Asian population. Summary statistics of AAs were obtained from different databases. Inverse variance weighted (IVW), weighted-mode, weighted median, MR-Egger, and MR-PRESSO methods were used to examine the potential causal association of UA with AAs. The IVW estimates indicated that elevated UA level was associated with higher AAA risk among the European population (OR = 1.315, 95%CI: 1.024–1.689). In the Asian population, the UA level was positively linked to the odds of AA (OR = 1.393, 95%CI: 1.061–1.829). In addition, sensitivity analyses through MR leave-one-out and single SNP effect methods showed that these results were relatively robust. UA may be a potential risk factor for AAs, indicating that clinicians should focus on serum UA levels among populations with high-risk of AAs. Studies to reveal the true relationship between them and clarify the underlying mechanism are still needed in the future.本研究基于孟德尔随机化（Mendelian randomization, MR）方法，旨在探究血清尿酸（uric acid, UA）水平与主动脉瘤（aortic aneurysms, AAs）之间的因果关联。本次MR研究中，研究数据取自两项全基因组关联研究（genome-wide association study, GWAS）荟萃分析：针对欧洲人群的英国生物库（UK Biobank, UKB）队列，以及针对亚洲人群的日本生物库项目（Biobank Japan Project, BBJ）队列，从中提取了尿酸水平与痛风相关数据；主动脉瘤的汇总统计量则来自多个独立数据库。本研究采用逆方差加权（inverse variance weighted, IVW）、加权众数法、加权中位数法、MR-Egger以及MR-PRESSO等方法，检验尿酸与主动脉瘤之间潜在的因果关联。逆方差加权分析结果显示，欧洲人群中尿酸水平升高与腹主动脉瘤（abdominal aortic aneurysms, AAA）风险升高显著相关（OR=1.315，95%CI：1.024–1.689）。在亚洲人群中，尿酸水平与主动脉瘤患病风险呈正相关（OR=1.393，95%CI：1.061–1.829）。此外，通过MR留一法及单SNP效应方法开展的敏感性分析结果显示，本研究结论具备较好的稳健性。本研究表明尿酸可能是主动脉瘤的潜在危险因素，提示临床医师应关注主动脉瘤高风险人群的血清尿酸水平。未来仍需开展相关研究以明确二者间的真实关联，并阐明其潜在的分子机制。