Late-onset Alzheimers disease (LOAD) is a multifactorial disease with the potential involvement of multiple genes. Complex diseases such as LOAD have a large affect on public health due to the significant financial burden of health care for these individuals. Genetics plays a significant role in the etiology of the disease, therefore it is of public health importance that the genetics of LOAD be investigated. There is a known association between APOE gene variants and LOAD. No additional genes have been consistently demonstrated to be associated with risk of LOAD. Multiple recent genome-wide association studies (GWAS) have found variants showing significant association with LOAD. Twelve SNPs were chosen from four GWAS for a replication study to determine if the associations seen between SNPs and AD risk in the respective studies were present in our population. Ten additional positional candidate SNPs were chosen on chromosome 10 because of observed linkage peaks for AD and predicted imprinted genes in this region. We genotyped these 22 SNPs as well the E2/E3/E4 APOE polymorphism in up to 993 Caucasian Americans with LOAD and up to 976 age-matched healthy Caucasian Americans. Our data showed no statistically significant associations between the 22 SNPs examined and the risk of AD. Stratification by APOE*4 carrier status also failed to reveal statistically significant associations. Additional analyses were performed to examine the potential associations between the 22 SNPs and age-at-onset, disease duration, and baseline MMSE score. The analysis revealed significant associations between two SNPs, rs3746319 (p=0.002) and rs16934131 (p=0.045), and age-at-onset. One SNP, rs16934131 (p=0.0002), was found to be significantly associated with disease duration. Three SNPs, rs16934131 (p=0.002), rs12781609 (p=0.012), and rs5984894 (p=0.009), were found to be associated with baseline MMSE score in controls. Of note, rs16934131, demonstrated statistically significant association with age at onset, disease duration, and MMSE score. Further study may be necessary to definitively rule out associations between these variants and LOAD.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04062010-135719 |
| Date | 28 June 2010 |
| Creators | Burns, Lauren Christina |
| Contributors | Dr. David Finegold, Dr. M. Michael Barmada, Dr. M. Ilyas Kamboh |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04062010-135719/ |
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