Homocysteine and small vessel stroke: A mendelian randomization analysis

Annals of Neurology
Susanna C LarssonHugh S Markus

Abstract

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. We used summary statistics data for single-nucleotide polymorphisms (SNPs) associated with tHcy (n = 18), folate (n = 3), vitamin B6 (n = 1), and vitamin B12 (n = 14) levels, and the corresponding data for stroke from the MEGASTROKE consortium (n = 16,952 subtyped ischemic stroke cases and 404,630 noncases). Genetically predicted tHcy was associated with SVS, with an odds ratio of 1.34 (95% confidence interval [CI], 1.13-1.58; p = 6.7 × 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 B6 levels were 0.49 (95% CI, 0.34-0.71; p = 1.3 × 10-4 ) and 0.70 (9...Continue Reading

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Citations

Jun 4, 2020·The American Journal of Clinical Nutrition·Pinpin Long, An Pan
Mar 17, 2020·Journal of Neurology·Huan CaiHao Zhang
Aug 20, 2019·Annual Review of Pharmacology and Toxicology·Anne Joutel
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Apr 11, 2021·British Journal of Cancer·Shuai YuanSusanna C Larsson
Aug 18, 2021·Stroke; a Journal of Cerebral Circulation·Marios K Georgakis, Dipender Gill

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Software Mentioned

R Foundation
PhenoScanner
VITATOPS
MEGASTROKE
Stata R

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