Eur J Neurol. 2021 Nov 19. doi: 10.1111/ene.15190. Online ahead of print.
ABSTRACT
BACKGROUND: The causal effect of insulin resistance on small vessel stroke and Alzheimer Disease was controversial in previous studies. We therefore applied Mendelian randomization (MR) analyses to identify causal effect of insulin resistance on small vessel stroke and Alzheimer’s disease (AD).
METHODS: We selected 12 single-nucleotide polymorphisms (SNPs) associated with fasting insulin levels and 5 SNPs associated with gold standard measures of insulin resistance as instrumental variables in MR analyses. Summary statistical data of SNP-small vessel stroke and of SNP-AD associations were derived from the MEGASTROKE and PGC-ALZ of 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 methods.
RESULTS: Genetically predicted higher insulin resistance had a higher odds ratio (OR) of small vessel stroke [OR 1.23; 95% confidence intervals (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 measure 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: Our findings provide a genetic support for potential causal effect of insulin resistance on small vessel stroke and AD.
PMID:34797599 | DOI:10.1111/ene.15190
