Hu Weiran, Zhang Kai, Yang Guang, Wang Haoxu, Gao Yanzheng
Department of Spinal Cord Surgery, Henan Provincial People's Hospital, Zhengzhou, China.
People's Hospital of Zhengzhou University, Henan, China.
SAGE Open Med. 2025 Apr 26;13:20503121251335513. doi: 10.1177/20503121251335513. eCollection 2025.
Previous observational studies reported that ankylosing spondylitis is closely related to hypertension. However, it is still controversial whether the association between ankylosing spondylitis and hypertension is causal. The effects of ankylosing spondylitis on diastolic and systolic blood pressure deserve further investigation. The objective of our study is to explore whether ankylosing spondylitis is causally associated with blood pressure.
A bidirectional two-sample Mendelian randomization (MR) analysis was performed by employing five Mendelian randomization analysis methods. MR Egger regression, weighted median, inverse variance weighted, and weight mode methods were performed in the two-sample Mendelian randomization analysis. We performed Mendelian randomization to investigate the association between ankylosing spondylitis (finn-b-M13_ANKYLOSPON) and hypertension (ukb-b-14057), diastolic blood pressure (ebi-a-GCST90000062) and systolic blood pressure (ebi-a-GCST90000059). We also performed reverse Mendelian randomization between exposures and outcomes. Another new validation cohort (ukb-b-18194) was also performed. The heterogeneity, horizontal pleiotropy, and possible outliers were examined in the MR analysis results.
The inverse variance weighted results showed that ankylosing spondylitis has no genetic causal relationship with hypertension ( = 0.441, OR = 1.001, 95% CI: 0.999-1.002). The inverse variance weighted results showed that ankylosing spondylitis has no genetic causal relationship with systolic blood pressure ( = 0.301, OR = 1.006, 95% CI: 0.995-1.018). The inverse variance weighted results showed that ankylosing spondylitis has no genetic causal relationship with diastolic blood pressure ( = 0.778, OR = 1.002, 95% CI: 0.988-1.016). The reverse Mendelian randomization between exposures and outcomes is negative. Another new validation cohort also confirmed the results. No heterogeneity was observed by the MR-pleiotropy residual sum and outlier test. The "leave-one-out" analysis indicated that the results of MR analysis were not affected by a single nucleotide polymorphism.
This study represents the first two-sample Mendelian randomization analysis aimed at investigating the causal genetic relationship between ankylosing spondylitis and blood pressure. Our Mendelian randomization analysis results revealed a lack of causal association between ankylosing spondylitis and hypertension, diastolic blood pressure, as well as systolic blood pressure.
既往观察性研究报告称强直性脊柱炎与高血压密切相关。然而，强直性脊柱炎与高血压之间的关联是否为因果关系仍存在争议。强直性脊柱炎对舒张压和收缩压的影响值得进一步研究。我们研究的目的是探讨强直性脊柱炎与血压之间是否存在因果关联。
采用五种孟德尔随机化分析方法进行双向两样本孟德尔随机化（MR）分析。在两样本孟德尔随机化分析中进行了MR埃格回归、加权中位数、逆方差加权和权重模式方法。我们进行孟德尔随机化以研究强直性脊柱炎（finn-b-M13_ANKYLOSPON）与高血压（ukb-b-14057）、舒张压（ebi-a-GCST90000062）和收缩压（ebi-a-GCST90000059）之间的关联。我们还在暴露因素和结局之间进行了反向孟德尔随机化。另外还进行了一个新的验证队列（ukb-b-18194）。在MR分析结果中检查了异质性、水平多效性和可能的异常值。
逆方差加权结果显示强直性脊柱炎与高血压无遗传因果关系（=0.441，OR=1.001，95%CI：0.999-1.002）。逆方差加权结果显示强直性脊柱炎与收缩压无遗传因果关系（=0.301，OR=1.006，95%CI：0.995-1.018）。逆方差加权结果显示强直性脊柱炎与舒张压无遗传因果关系（=0.778，OR=1.002，95%CI：0.988-1.016）。暴露因素和结局之间的反向孟德尔随机化结果为阴性。另一个新的验证队列也证实了该结果。MR多效性残差和异常值检验未观察到异质性。“留一法”分析表明MR分析结果不受单个单核苷酸多态性的影响。
本研究是首个旨在研究强直性脊柱炎与血压之间因果遗传关系的两样本孟德尔随机化分析。我们的孟德尔随机化分析结果显示强直性脊柱炎与高血压、舒张压以及收缩压之间缺乏因果关联。
