Abstract Details

Title Association of GWAS Loci with Alzheimer's Disease in China

Topic Aging and Dementia

Presentation(s) S34 - (-)

Poster/Presentation
Number 002

Objective

Background Five GWAS in the Caucasian populations have recently identified and confirmed 9 novel AD susceptibility loci (CLU, CR1, PICALM, BIN1, ABCA7, MS4A gene cluster, CD2AP, CD33 and EPHA1). These studies have been conducted almost exclusively in Caucasian populations and it is unclear whether these observations generalize to populations with different ethnicities.

Design/Methods We recruited 1, 224 unrelated Northern Han Chinese individuals comprising 612 patients with a clinical diagnosis of LOAD and 612 healthy age- and sex-matched controls. Because to our previous study investigating CLU, CR1 and PICALM in the Han population, we limited the present analysis to BIN1, ABCA7, MS4A gene cluster, CD2AP, CD33 and EPHA1.

Results In a multivariate analysis, associations of MS4A6A (rs610932; OR=0.632, Bonferroni corrected P=0.019) and CD33 (rs3865444; OR=1.492, Bonferroni corrected P=0.017) with LOAD were successfully replicated. When these data were stratified by the APOE ?4 status, both rs610932 and rs610932 were evident only among subjects without the APOE ?4 allele. For BIN1, assuming a dominant model of inheritance, a positive association for rs7561528 in APOE ?4 carriers was observed. This association, however, did not remain significant after Bonferroni correction. As for ABCA7, CD2AP and EPHA1 SNPs from recent GWAS, despite the similar directional effects, no significant differences in genotype and estimated allele frequency distribution between patients and controls were observed.

Conclusions This study provides the first independent evidence that MS4A and CD33 loci are associated with the risk of LOAD in the Northern Han Chinese population. Genotypes at the two loci confer risk predominantly in APOE ?4-nagetive subjects. However, BIN1, ABCA7, CD2AP and EPHA1 SNPs from recent GWAS might not play major roles in the genetic predisposition to LOAD in this population.

Authors/Disclosures
Jin-Tai Yu PRESENTER	No disclosure on file
Lan Tan (Affiliated Hospital of Qingdao Medical College)	No disclosure on file
Maria Pia Sormani (University of Genoa)	Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Geneuro. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic. Maria Pia Sormani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche.

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