Oct 21, 2017

Branched-chain amino acids and Alzheimer's disease: a Mendelian randomization analysis

Scientific Reports
Susanna C Larsson, Hugh S Markus

Abstract

We conducted a two-sample Mendelian randomization study to test the hypothesis that raised plasma levels of the branched-chain amino acids isoleucine, leucine, and valine are associated with Alzheimer's disease (AD). From a genome-wide association study of 16,596 individuals of European ancestry, we obtained summary statistics for four independent single nucleotide polymorphisms (SNPs) associated with isoleucine levels and one SNP associated with both leucine and valine levels at genome-wide significance. Summary statistics of the associations of the five SNPs with AD were obtained from the International Genomics of Alzheimer's Project (17,008 AD cases and 37,154 controls). Based on four SNPs, the odds ratio of AD per genetically predicted one standard deviation higher isoleucine levels was 1.35 (95% CI, 1.08-1.69; p = 0.007). The leucine- and valine-raising allele was not associated with AD (p = 0.46). These data suggest that a genetic predisposition to raised plasma isoleucine levels is positively associated with AD.

Mentioned in this Paper

Genome-Wide Association Study
Mendelian Randomization Analysis
Genome
Valine
Alzheimer's Disease
Genomics
Isoleucine Measurement
Plasma
APP
Isoleucine

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