Abstract Details

Title GWAS Top Hits Correlate with the Patterns of Cognitive Impairment in Alzheimer Disease

Topic Aging and Dementia

Presentation(s) P04 - (-)

Poster/Presentation
Number 226

Objective

Background BACKGROUND: GWAS have discovered several genetic variations as susceptibility loci for late-onset AD.

Design/Methods DESIGN/METHODS: We selected 86 single nucleotide polymorphisms (SNPs) selected from 12 genes (ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, LRAT, MS4A6A, PCDH11X, and PICALM) and genotyped in 290 AD cases. These 12 genes were selected based on results of the recent GWAS that reported AD-susceptibility loci, and the selected genes included AlzGene top results (http://www.alzgene.org). Additional tag SNPs (minor allele frequency ? 0.05) were selected for 12 selected genes using the HapMap JPT and CHB samples. We also analyzed clinical data of 211 AD patients who underwent neuropsychological evaluations using the Seoul Neuropsychological Screening Battery (SNSB) that assesses five cognitive domains: attention, memory, language, visuospatial function, and frontal/executive function. We performed multiple regression analyses with the adjustment for age at neuropsychological evaluation, sex, disease duration, and education duration.

Results RESULTS: There were four significant associations between genotypes and phenotypes of AD patients. The CR1 SNP rs11803956 correlated with K-MMSE score (r = 1.718, P = 1.8 [times] 10-5); APOE SNP rs2075650 correlated with the percentile of total score in phonemic fluency (r = 11.146, P = 2.0 [times] 10-4) and the percentile of Rey complex figure test (RCFT) copy score (r = -6.861, P = 4.0 [times] 10-5); ABCA7 SNP rs3752232 correlated with RCFT copy score (r = 15.636, P = 1.4 [times] 10-4). These correlations remained significant after Bonferroni correction.

Conclusions CONCLUSIONS: We found that three GWAS top hits significantly correlated with specific aspects of cognitive impairments in AD patients. These findings may provide new impetus for focused studies aimed at understanding the pathogenesis of AD.

Authors/Disclosures
Sun Ju Chung, MD, PhD, FAAN (Neurology, Asan Medical Center) PRESENTER	Dr. Chung has nothing to disclose.
	No disclosure on file
	No disclosure on file
Soo Y. You, MD	No disclosure on file
	No disclosure on file
Jae-Hong Lee, MD	No disclosure on file
Michael D. Geschwind, MD, PhD, FAAN (UCSF)	Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Brainstorm Cell Therapeutics, Inc.. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Walter Grubb. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lehrman Group. Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Reata Pharmaceuticals, Inc..
Michael D. Geschwind, MD, PhD, FAAN (UCSF)	Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Brainstorm Cell Therapeutics, Inc.. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Walter Grubb. Dr. Geschwind has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lehrman Group. Dr. Geschwind has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Reata Pharmaceuticals, Inc..
Timothy J. Turner	Timothy J. Turner has received personal compensation for serving as an employee of Sanofi. Timothy J. Turner has stock in Sanofi. Timothy J. Turner has received intellectual property interests from a discovery or technology relating to health care.

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