Frontiers in Genetics (Jul 2024)

Mendelian randomization of stroke risk after total hip and knee replacements

  • Liang Pang,
  • Zhihui Zheng,
  • Pingping Su,
  • Zhouhengte Xu,
  • Yirui Chen,
  • Zhicheng Liao,
  • Pengcheng Jia,
  • Xiuling Zhang,
  • Cunxian Lv

DOI
https://doi.org/10.3389/fgene.2024.1435124
Journal volume & issue
Vol. 15

Abstract

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ObjectivePrevious epidemiological studies have indicated an increased risk of neurovascular diseases in patients following total hip and knee replacements. However, definitive conclusions regarding the increased risk of stroke post-replacement remain elusive. Therefore, we conducted a two-sample Mendelian randomization study to investigate the causal relationship between total hip and knee replacements and stroke.MethodsWe utilized summary data from publicly available genome-wide association studies (GWAS). Data concerning total hip replacements (THR, N = 319,037) and total knee replacements (TKR, N = 252,041) were sourced from the Genetics of Osteoarthritis (GO) Consortium. Stroke-related data were obtained from the International Stroke Genetics Consortium, encompassing any stroke (AS), any ischemic stroke (AIS), large vessel ischemic stroke (LV-IS), cardioembolic ischemic stroke (CE-IS), and small vessel ischemic stroke (SV-IS). Our primary causal inference method was the inverse variance weighted (IVW) approach, supplemented by weighted median and MR-Egger regression as secondary inference methods. We utilized the MR-PRESSO global test for outlier detection, Cochran’s Q statistic to assess heterogeneity, and assessed the multiplicity and stability of our findings using p-values from MR-PRESSO and MR-Egger regressions, and the leave-one-out method, respectively.ResultsWe identified significant genetic associations between THR and both AS (IVW p = 0.0001, OR = 1.08, 95% CI = 1.04–1.12) and AIS (IVW p = 0.0016, OR = 1.07, 95% CI = 1.03–1.12). Significant associations were also observed between TKR and AS (IVW p = 0.0002, OR = 1.08, 95% CI = 1.04–1.12), as well as AIS (IVW p = 0.0005, OR = 1.15, 95% CI = 1.06–1.24).ConclusionOur findings genetically support an increased risk of stroke following total hip and knee replacements. However, further studies are necessary to elucidate the specific mechanisms underlying stroke episodes post-replacement.

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