Abstract Details

Title Identification of Novel Genetic Variants by an Exome Array in Alzheimer Disease

Topic Aging and Dementia

Presentation(s) (-)

Poster/Presentation
Number 005

Objective

Background Genetic variants so far identified by genome-wide association studies (GWAS) explain only a small fraction of the overall inherited risk of AD.

Design/Methods We genotyped 295,988 genetic variants in 1,005 subjects (400 late-onset AD cases and 605 normal elderly controls) using Axiom Exome Array. All cases and normal controls were ethnic Koreans. The exome array was based on genomic content derived from a pool of variants discovered in over 16 major human exome sequencing initiatives, including the NHLBI Exome Project, the Genetics of Type 2 Diabetes program, the 1000 Genomes Project, and others. The variants included in the exome array were ascertained by sequencing [sim]12,000 ethnically diverse samples at 20x coverage or higher. Genotype calling was performed with the Axiom GT1 Algorithm. Cochran-Armitage trend test was used as a primary analysis.

Results The 241,043 (83.2%) variants of 295,988 genetic variants showed the minor allele frequencies of less than 5% in normal controls, and 179,866 (62.1%) genetic variants showed minor allele frequencies of 0% in our sample and excluded from analysis. Of 97,397 informative genetic variants, seven genetic variants showed significant associations with late-onset AD and these associations remained significant after the Bonferroni correction. The TOMM40 SNP rs2075650 had the most significant association with late-onset AD (p < 1.0 [times] 10-32). Two additional variants in APOE gene and four novel variants in other four genes (each one in APOC1, LOC1720, OSBPL6, and SETX genes) showed significant associations with late-onset AD.

Conclusions Our results identified novel genetic loci associated with late-onset AD. Further study using independent samples and functional analysis is needed to confirm these findings.

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
	No disclosure on file
Soo Y. You, MD	No disclosure on file
Laura J. Balcer, MD, MSCE, FAAN (NYU Grossman School of Medicine)	Dr. Balcer has received personal compensation for serving as an employee of North American Neuro-Ophthalmology Society. An immediate family member of Dr. Balcer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Children's Hospital of Philadelphia.
	No disclosure on file
Jae-Hong Lee, MD	No disclosure on file

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