RT Journal Article
SR Electronic
T1 A Mendelian randomisation, propensity score matching study to investigate causal association between serum homocysteine and intracranial aneurysm
JF Stroke and Vascular Neurology
JO Stroke Vasc Neurol
FD BMJ Publishing Group Ltd
SP 202
OP 211
DO 10.1136/svn-2023-002414
VO 9
IS 3
A1 Wen, Zhuohua
A1 Feng, Xin
A1 Tong, Xin
A1 Peng, Chao
A1 Xu, Anqi
A1 Fan, Haiyan
A1 Bi, Yiming
A1 Liu, Wenchao
A1 Li, Zhenjun
A1 Guo, Shenquan
A1 Jin, Fa
A1 Li, Ran
A1 Liu, Yanchao
A1 Su, Shixing
A1 Zhang, Xin
A1 Li, Xifeng
A1 He, Xuying
A1 Liu, Aihua
A1 Duan, Chuanzhi
YR 2024
UL http://svn.bmj.com/content/9/3/202.abstract
AB Background and purpose Recent observational studies have reported that serum total homocysteine (tHcy) is associated with intracranial aneurysms (IAs). However, the causal effect of tHcy on IAs is unknown. We leveraged large-scale genetic association and real-world data to investigate the causal effect of tHcy on IA formation.Methods We performed a two-sample Mendelian randomisation (MR) using publicly available genome-wide association studies summary statistics to investigate the causal relationship between tHcy and IAs, following the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology-MR statement. Furthermore, a propensity score matching (PSM) analysis was conducted to evaluate the detailed effects of tHcy on risk of IA formation by utilizing real-world multicentre data, including 9902 patients with and without IAs (1:1 matched). Further interaction and subgroup analyses were performed to elucidate how tHcy affects risk of IA formation.Results MR analyses indicated that genetically determined tHcy was causally associated with IA risk (OR, 1.38, 95% CI 1.07 to 1.79; p=0.018). This is consistent with the more conservative weighted median analysis (OR, 1.41, 95% CI 1.03 to 1.93; p=0.039). Further sensitivity analyses showed no evidence of horizontal pleiotropy or heterogeneity of single nucleotide polymorphisms in causal inference. According to the PSM study, we found that, compared with low tHcy (≤15 µmol/L), moderate tHcy (>15–30 µmol/L) (OR 2.13, 95% CI 1.93 to 2.36) and high tHcy (>30 µmol/L) (OR 3.66, 95% CI 2.71 to 4.95) were associated with a higher IA risk (p trend <0.001). Subgroup analyses demonstrated significant ORs of tHcy in each subgroup when stratified by traditional cardiovascular risk factors. Furthermore, there was also a synergistic effect of tHcy and hypertension on IA risk (p interaction <0.001; the relative excess risk due to interaction=1.65, 95% CI 1.29 to 2.01).Conclusion Both large-scale genetic evidence and multicentre real-world data support a causal association between tHcy and risk of IA formation. Serum tHcy may serve as a biomarker to identify high-risk individuals who would particularly benefit from folate supplementation.Data are available upon reasonable request and contacting the correspondent authors.