How to cite this article as follows: Burns LC, Minster RL, Demirci FY, Barmada MM, Ganguli M, Lopez OL, DeKosky ST, Kamboh MI. 2011. Replication Study of Genome-Wide Associated SNPs With Late-Onset Alzheimer's Disease. Am J Med Genet Part B 156:507–512.
Replication study of genome-wide associated SNPs with late-onset Alzheimer's disease†
Article first published online: 7 APR 2011
Copyright © 2011 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 156, Issue 4, pages 507–512, June 2011
How to Cite
Burns, L.C., Minster, R.L., Demirci, F.Y., Barmada, M.M., Ganguli, M., Lopez, O.L., DeKosky, S.T. and Kamboh, M.I. (2011), Replication study of genome-wide associated SNPs with late-onset Alzheimer's disease. Am. J. Med. Genet., 156: 507–512. doi: 10.1002/ajmg.b.31194
- Issue published online: 25 APR 2011
- Article first published online: 7 APR 2011
- Manuscript Accepted: 14 MAR 2011
- Manuscript Received: 24 MAY 2010
- National Institute on Aging. Grant Numbers: AG030653, AG005133, AG07562
- Alzheimer's disease;
- genome-wide association studies;
- disease duration
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. © 2011 Wiley-Liss, Inc.