%0 Journal Article
%T Mendelian randomization of stroke risk after total hip and knee replacements.
%A Pang L
%A Zheng Z
%A Su P
%A Xu Z
%A Chen Y
%A Liao Z
%A Jia P
%A Zhang X
%A Lv C
%J Front Genet
%V 15
%N 0
%D 2024
%M 39055256
%F 4.772
%R 10.3389/fgene.2024.1435124
%X <B>UNASSIGNED: </B>Previous 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.<BR><B>UNASSIGNED: </B>We 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.<BR><B>UNASSIGNED: </B>We 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).<BR><B>UNASSIGNED: </B>Our 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.