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Replication study of genome-wide associated SNPs with late-onset Alzheimer's disease.

Authors: Burns, LC  Minster, RL  Demirci, FY  Barmada, MM  Ganguli, M  Lopez, OL  DeKosky, ST  Kamboh, MI 
Citation: Burns LC, etal., Am J Med Genet B Neuropsychiatr Genet. 2011 Jun;156B(4):507-12. doi: 10.1002/ajmg.b.31194. Epub 2011 Apr 7.
Pubmed: (View Article at PubMed) PMID:21480501
DOI: Full-text: DOI:10.1002/ajmg.b.31194

Late-onset Alzheimer's disease (LOAD) is a multifactorial disease with the potential involvement of multiple genes. Four recent genome-wide association studies (GWAS) have found variants showing significant association with LOAD on chromosomes 6, 10, 11, 12, 14, 18, 19, and on the X chromosome. We examined a total of 12 significant SNPs from these studies to determine if the results could be replicated in an independent large case-control sample. We genotyped these 12 SNPs as well the E2/E3/E4 APOE polymorphisms in up to 993 Caucasian Americans with LOAD and up to 976 age-matched healthy Caucasian Americans. We found no statistically significant associations between the 12 SNPs and the risk of AD. Stratification by APOE*4 carrier status also failed to reveal statistically significant associations. Additional analyses were performed to examine potential associations between the 12 SNPs and age-at-onset (AAO) and disease duration among AD cases. Significant associations were observed between AAO and ZNF224/rs3746319 (P = 0.002) and KCNMA1/rs16934131 (P = 0.0066). KCNMA1/rs16934131 also demonstrated statistically significant association with disease duration (P = 0.0002). Although we have been unable to replicate the reported GWAS association with AD risk in our sample, we have identified two new associations with AAO and disease duration that need to be confirmed in additional studies.


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CRRD Object Information
CRRD ID: 10412025
Created: 2015-11-11
Species: All species
Last Modified: 2015-11-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.