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Branched-chain amino acids and Alzheimer's disease: a Mendelian randomization analysis.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.ORCID iD: 0000-0003-0118-0341
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 1, article id 13604Article in journal (Refereed) Published
Abstract [en]

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; pā€‰=ā€‰0.007). The leucine- and valine-raising allele was not associated with AD (pā€‰=ā€‰0.46). These data suggest that a genetic predisposition to raised plasma isoleucine levels is positively associated with AD.

Place, publisher, year, edition, pages
2017. Vol. 7, no 1, article id 13604
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Medical Genetics
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URN: urn:nbn:se:uu:diva-397269DOI: 10.1038/s41598-017-12931-1PubMedID: 29051501OAI: oai:DiVA.org:uu-397269DiVA, id: diva2:1371151
Available from: 2019-11-19 Created: 2019-11-19 Last updated: 2020-01-16Bibliographically approved

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