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A Candidate Gene Study of Late-Onset Alzheimer's Disease

Burns, Lauren Christina (2010) A Candidate Gene Study of Late-Onset Alzheimer's Disease. Master's Thesis, University of Pittsburgh. (Unpublished)

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Late-onset Alzheimer's 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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Burns, Lauren Christinalcb18@pitt.eduLCB18
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKamboh, M Ilyaskamboh@pitt.eduKAMBOH
Committee MemberFinegold, Daviddavid.finegold@mail.hgen.pitt.eduDNF
Committee MemberBarmada, M Michaelbarmada@pitt.eduBARMADA
Date: 28 June 2010
Date Type: Completion
Defense Date: 13 April 2010
Approval Date: 28 June 2010
Submission Date: 6 April 2010
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Alzheimer's Disease; biological candidate; GWAS; MMSE score; positional candidate; putative imprinted genes; replication study; age at onset; disease duration
Other ID:, etd-04062010-135719
Date Deposited: 10 Nov 2011 19:34
Last Modified: 15 Nov 2016 13:38


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