Genetically Determined Serum Uric Acid and Alzheimer's Disease Risk

Journal of Alzheimer's Disease : JAD
Hongjuan Yuan, Wenjie Yang

Abstract

To evaluate whether genetically increased serum uric acid levels influence the risk of Alzheimer's disease (AD), we used genome-wide significant single nucleotide polymorphisms for uric acid as the instrumental variables, and undertook a Mendelian randomization (MR) study to estimate the effect of uric acid on the risk of AD. The MR method prevents bias due to reverse causation (e.g., uric acid changes because of AD) and minimizes bias due to confounding of both measured and unmeasured confounders. We used the summary statistics from The International Genomics of Alzheimer's Project Consortium that is the largest AD genome-wide association study of 74,046 individuals of European ethnicity including 25,580 AD cases. We further performed sensitivity analyses to evaluate the assumptions of the MR method. The MR analyses did not support a causal role of genetically elevated serum uric acid on AD risk (odds ratio: 1.02, 95% confidence interval: 0.93-1.12, p = 0.65). Sensitivity analyses, including MR-Egger regression, suggested no strong evidence of bias due to pleiotropy. In conclusion, lifelong genetically increased serum uric acid levels have no protective effect on the risk of AD.

Citations

Oct 6, 1997·BMJ : British Medical Journal·M EggerC Minder
Apr 14, 2006·European Heart Journal·Carmelinda RuggieroLuigi Ferrucci
Mar 28, 2007·Analytica Chimica Acta·Hossam M NassefCiara O'Sullivan
Sep 22, 2007·Statistics in Medicine·Debbie A LawlorGeorge Davey Smith
Jul 5, 2008·Nucleosides, Nucleotides & Nucleic Acids·Yuri Y Sautin, Richard J Johnson
Nov 28, 2008·Brain : a Journal of Neurology·S M EuserMonique M B Breteler
Aug 19, 2011·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Markus DonixSusan Y Bookheimer
Apr 6, 2012·Diabetology & Metabolic Syndrome·Erick Prado de Oliveira, Roberto Carlos Burini
Jun 7, 2012·Journal of Alzheimer's Disease : JAD·Robyn A HoneaAlzheimer’s Disease Neuroimaging Initiative
Oct 12, 2013·Genetic Epidemiology·Stephen BurgessSimon G Thompson
Mar 6, 2015·Annals of the Rheumatic Diseases·Na LuHyon K Choi
May 21, 2015·Nature Reviews. Neuroscience·Frank L HeppnerBurkhard Becher
Jun 8, 2015·International Journal of Epidemiology·Jack BowdenStephen Burgess
Aug 19, 2015·Statistical Methods in Medical Research·Stephen BurgessSimon G Thompson
Sep 1, 2015·International Journal of Cardiology·Jessica MaiuoloVincenzo Mollace
Dec 20, 2015·Journal of Alzheimer's Disease : JAD·Samantha L GardenerRalph N Martins
Jan 30, 2016·Journal of the American College of Cardiology·Tanya KeenanDanish Saleheen
Nov 20, 2016·Neurology·Lauren E MokryJ Brent Richards
Jul 5, 2018·Genetic Epidemiology·Fernando Pires HartwigGeorge Davey Smith

Related Concepts

Genome-Wide Association Study
Familial Alzheimer Disease (FAD)
Mendelian Randomization Analysis
Magnetic Resonance Imaging
Genome
Urate
Genetic Pleiotropy
Alzheimer's Disease
Evaluation
Genomics

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