Journal
ANNALS OF TRANSLATIONAL MEDICINE
Volume 6, Issue 22, Pages -Publisher
AME PUBL CO
DOI: 10.21037/atm.2018.07.05
Keywords
Alzheimer's Disease Neuroimaging initiative 1 (ADNI-1); Alzheimer's disease (AD); fluorodeoxyglucose f18 (18F-FDG); RNA-binding Fox1 (RBFOX1)
Categories
Funding
- ADNI
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimers Association
- Alzheimers Drug Discovery Foundation
- BioClinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Company
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- F. Hoffmann-La Roche Ltd
- Genentech, Inc
- GE Healthcare
- Innogenetics, N.V.
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC
- Medpace, Inc.
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Synarc Inc.
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
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Background: Fluorodeoxyglucose f18 positron emission tomography (18F-FDG PET) is regarded as the only functional neuroimaging biomarker for degeneration which can be used to increase the certainty of Alzheimer's disease (.AD) pathophysiological process in research settings or as an optional clinical tool where available. Although a decline in FDG metabolism was confirmed in some regions known to be associated with AD, there was little known about the genetic association of FDG metabolism in AD cohorts. In this study, we present the first genome-wide association study (GWAS) analysis of brain FDG metabolism. Methods: A total of 222 individuals were included from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort. All subjects were restricted to non-Hispanic Caucasians and met all quality control (QC) criteria. Associations of 18F-FDG with the genetic variants were assessed using PLINK 1.07 under the additive genetic model. Genome-wide associations were visualized using a software program R 3.2.3. Results: One significant SNP rs12444565 in RNA-binding Fox 1 (RBFOX1) was found to have a strong association with 18F-FDG (P=6.06x10(-8)). Rs235141, rs79037, rs12526331 and rs12529764 were identified as four suggestive loci associated with 18F-FDG. Conclusions: Our study results suggest that a genome-wide significant SNP (rs12444565) in the RBFOX1, and four suggestive loci (rs235141, rs79037, rs12526331 and rs12529764) arc associated with 18F-FDG.
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