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- Larsson, Susanna C., et al.
(författare)
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Homocysteine and small vessel stroke : A mendelian randomization analysis
- 2019
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 85:4, s. 495-501
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Tidskriftsartikel (refereegranskat)abstract
- Objective Trials of B vitamin therapy to lower blood total homocysteine (tHcy) levels for prevention of stroke are inconclusive. Secondary analyses of trial data and epidemiological studies suggest that tHcy levels may be particularly associated with small vessel stroke (SVS). We assessed whether circulating tHcy and B vitamin levels are selectively associated with SVS, but not other stroke subtypes, using Mendelian randomization.MethodsWe used summary statistics data for single-nucleotide polymorphisms (SNPs) associated with tHcy (n = 18), folate (n = 3), vitamin B-6 (n = 1), and vitamin B-12 (n = 14) levels, and the corresponding data for stroke from the MEGASTROKE consortium (n = 16,952 subtyped ischemic stroke cases and 404,630 noncases).ResultsGenetically predicted tHcy was associated with SVS, with an odds ratio of 1.34 (95% confidence interval [CI], 1.13-1.58; p = 6.7 x 10(-4)) per 1 standard deviation (SD) increase in genetically predicted tHcy levels, but was not associated with large artery or cardioembolic stroke. The association was mainly driven by SNPs at or near the MTHFR and MUT genes. The odds ratios of SVS per 1 SD increase in genetically predicted folate and vitamin B-6 levels were 0.49 (95% CI, 0.34-0.71; p = 1.3 x 10(-4)) and 0.70 (95% CI, 0.52-0.94; p = 0.02), respectively. Genetically higher vitamin B-12 levels were not associated with any stroke subtype.Interpretation These findings suggest that any effect of homocysteine-lowering treatment in preventing stroke will be confined to the SVS subtype. Whether genetic variants at or near the MTHFR and MUT genes influence SVS risk through pathways other than homocysteine levels and downstream effects require further investigation. Ann Neurol 2019;85:495-501
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| 2. |
- Larsson, Susanna C., et al.
(författare)
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Smoking and stroke : A mendelian randomization study
- 2019
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 86:3, s. 468-471
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Tidskriftsartikel (refereegranskat)abstract
- We used the Mendelian randomization design to explore the potential causal association of smoking with ischemic stroke and intracerebral hemorrhage using summary statistics data for 34,217 ischemic stroke cases and 404,630 noncases, and 1,545 cases of intracerebral hemorrhage and 1,481 noncases. Genetic predisposition to smoking initiation (ever smoking regularly), based on up to 372 single-nucleotide polymorphisms, was statistically significantly positively associated with any ischemic stroke, large artery stroke, and small vessel stroke but not cardioembolic stroke or intracerebral hemorrhage. This study provides genetic support for a causal association of smoking with ischemic stroke, particularly large artery and small vessel stroke. ANN NEUROL 2019;86:468-471
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| 3. |
- Yuan, Shuai, et al.
(författare)
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Circulating Lipoprotein Lipids, Apolipoproteins and Ischemic Stroke.
- 2020
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 88:6, s. 1229-1236
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We conducted a Mendelian randomization (MR) study to disentangle the comparative effects of lipids and apolipoproteins on ischemic stroke.METHODS: Single-nucleotide polymorphisms associated with low- and high-density lipoprotein (LDL and HDL) cholesterol, triglycerides, and apolipoprotein A-I and B (apoA-I and apoB) at the level of genomewide significance (p < 5 × 10-8 ) in the UK Biobank were used as instrumental variables. Summary-level data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium with 514,791 individuals (60,341 ischemic stroke cases, and 454,450 non-cases).RESULTS: Increased levels of apoB, LDL cholesterol, and triglycerides were associated with higher risk of any ischemic stroke, large artery stroke, and small vessel stroke in the main and sensitivity univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, apoB retained a robust effect (p < 0.05), whereas the estimate for LDL cholesterol was reversed, and that for triglycerides largely attenuated. Decreased levels of apoA-I and HDL cholesterol were robustly associated with increased risk of any ischemic stroke, large artery stroke, and small vessel stroke in all univariable MR analyses, but the association for apoA-I was attenuated to the null after mutual adjustment.INTERPRETATION: The present MR study reveals that apoB is the predominant trait that accounts for the etiological basis of apoB, LDL cholesterol, and triglycerides in relation to ischemic stroke, in particular large artery and small vessel stroke. Whether HDL cholesterol exerts a protective effect on ischemic stroke independent of apoA-I needs further investigation. ANN NEUROL 2020;88:1229-1236.
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