Ling-Li Kong1,2, Dan Miao2, Lin Tan2,3, Shu-Lei Liu4, Jie-Qiong Li2, Xi-Peng Cao3, Lan Tan2. 1. Department of Geriatric Psychiatry, Qingdao Mental Health Center, Qingdao University, Qingdao 266071, China. 2. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China. 3. Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China. 4. Department of Neurology, Qingdao Center Hospital, Qingdao 266000, China.
Abstract
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 Fox1 (RBFOX1) was found to have a strong association with 18F-FDG (P=6.06×10-8). 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) are associated with 18F-FDG.
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 Fox1 (RBFOX1) was found to have a strong association with 18F-FDG (P=6.06×10-8). 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) are associated with 18F-FDG.
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