Abstract | BACKGROUND AND PURPOSE: METHODS: We selected 12 single-nucleotide polymorphisms (SNPs) associated with fasting insulin levels and five SNPs associated with "gold standard" measures of insulin resistance as instrumental variables in MR analyses. Summary statistical data on SNP-small vessel stroke and on SNP-AD associations were derived from studies by the Multi-ancestry Genome-Wide Association Study of Stroke consortium (MEGASTROKE) and the Psychiatric Genomics Consortium- Alzheimer Disease Workgroup (PGC-ALZ) in individuals of European ancestry. Two-sample MR estimates were conducted with inverse-variance-weighted, robust inverse-variance-weighted, simple median, weighted median, weighted mode-based estimator, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. RESULTS: Genetically predicted higher insulin resistance had a higher odds ratio (OR) of small vessel stroke (OR 1.23, 95% confidence interval [CI] 1.05-1.44, p = 0.01 using fasting insulin; OR 1.25, 95% CI 1.07-1.46, p = 0.006 using gold standard measures of insulin resistance) and AD (OR 1.13, 95% CI 1.04-1.23, p = 0.004 using fasting insulin; OR 1.02, 95% CI 1.00-1.03, p = 0.03 using gold standard measures of insulin resistance) using the inverse-variance-weighted method. No evidence of pleiotropy was found using MR-Egger regression. CONCLUSION:
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Authors | Mengyuan Zhou, Hao Li, Yongjun Wang, Yuesong Pan, Yilong Wang |
Journal | European journal of neurology
(Eur J Neurol)
Vol. 29
Issue 3
Pg. 698-706
(03 2022)
ISSN: 1468-1331 [Electronic] England |
PMID | 34797599
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 European Academy of Neurology. |
Topics |
- Alzheimer Disease
(complications, genetics)
- Genome-Wide Association Study
- Humans
- Insulin Resistance
(genetics)
- Mendelian Randomization Analysis
- Polymorphism, Single Nucleotide
(genetics)
- Stroke
(complications, genetics)
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