Dataset Information

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study.

ABSTRACT:

Objective

To investigate the link between genetic variants associated with plasma homocysteine levels and risk of intracranial aneurysm (IA) using two-sample Mendelian randomization.

Methods

We used single-nucleotide polymorphisms associated with human plasma homocysteine levels as instrumental variables for the primary analysis in a genome-wide association study of 44,147 subjects of European ancestry. Summary-level statistics were obtained for 79,429 individuals, including 7,495 IA cases and 71,934 controls. To enhance validity, five different Mendelian randomization methods (MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) were used for the analyses.

Results

The inverse variance weighted analysis method produced P-values of 0.398 for aneurysmal subarachnoid hemorrhage [odds ratio (OR): 1.104; 95% confidence interval (CI): 0.878-1.387], 0.246 for IA (OR: 1.124; 95% CI: 0.923-1.368), and 0.644 for unruptured IA (OR: 1.126; 95% CI: 0.682-1.858). The MR-Egger analysis showed no association between IAs and homocysteine, with all P > 0.05.

Conclusion

Using gene-related instrumental variables, the Mendelian randomization analyses demonstrated a lack of an association between plasma homocysteine levels and IAs or aneurysmal subarachnoid hemorrhage.

SUBMITTER: Ma C

PROVIDER: S-EPMC9554923 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study.

Ma Chencheng C Zhang Weiwei W Mao Lei L Zhang Guangjian G Shen Yuqi Y Chang Hanxiao H Xu Xiupeng X Li Zheng Z Lu Hua H

Frontiers in neurology 20220928

<h4>Objective</h4>To investigate the link between genetic variants associated with plasma homocysteine levels and risk of intracranial aneurysm (IA) using two-sample Mendelian randomization.<h4>Methods</h4>We used single-nucleotide polymorphisms associated with human plasma homocysteine levels as instrumental variables for the primary analysis in a genome-wide association study of 44,147 subjects of European ancestry. Summary-level statistics were obtained for 79,429 individuals, including 7,495 ...[more]

PMID: 36247759

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Project description:BackgroundIntracranial aneurysm (IA) accounts for a substantial source of non-traumatic subarachnoid hemorrhage, with inflammation postulated as a potential factor in its pathogenesis. The present study aims at evaluating the association between circulating inflammatory cytokines and risk of IA under a bidirectional two-sample Mendelian randomization (MR) design.MethodsFor primary analysis, summary statistics of inflammatory regulators was obtained from a genome-wide association study (GWAS) comprising 8293 Finnish participants. Summary data of IA were extracted from a GWAS which comprised 7495 cases and 71,934 controls in European descent. For targeted analysis, summary statistics were extracted from two proteomic studies, which recruit 3301 and 5368 European participants, respectively. Summary data of IA were acquired from FinnGen study with 5342 cases and 342,673 controls. We employed inverse variance weighted (IVW) method as main approach, with sensitivity analyses using weighted median, MR-Egger, and MR-PRESSO methods. Reverse MR analyses were conducted to minimize bias from reverse causality.ResultsNo causation of cytokines with IA subtypes was identified in both primary and targeted analysis after Bonferroni correction. In primary analysis, vascular endothelial growth factor (VEGF) and fibroblast growth factor basic (bFGF) levels were suggestively associated with aneurysmal subarachnoid hemorrhage (aSAH) [VEGF → aSAH: OR = 1.15, 95%CI 1.04-1.26, P = 0.005; bFGF → aSAH: OR = 0.62, 95% CI 0.42-0.92, P = 0.02]. Statistical significance failed to replicate in targeted analysis. Instead, suggestive protective effects for aSAH were identified in FGF-9 (FGF-9 → aSAH: OR = 0.74, 95% CI 0.62-0.89, P = 0.001) and FGF-16 (FGF-16 → aSAH: OR = 0.84, 95% CI 0.72-0.97, P = 0.017). Furthermore, reverse analyses identified suggestive effect of unruptured IA on RANTES, MIF, GRO-alpha, FGF-16, and FGF-19. Result remained robust after applying sensitivity tests.ConclusionsNo causality of inflammatory biomarkers on the risk of IA subtypes was identified. Future large-scale studies are in need to evaluate the temporal dynamics of cytokines in conjunction with IA.

Dataset Information

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study.

Objective

Methods

Results

Conclusion

Publications

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study.

Similar Datasets

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