Analysis of Copy Number Variation in Alzheimer's Disease in a Cohort of Clinically Characterized and Neuropathologically Verified Individuals

Shanker Swaminathan, Matthew J. Huentelman, Jason J. Corneveaux, Amanda J. Myers, Kelley M. Faber, Tatiana Foroud, Richard Mayeux, Li Shen, Sungeun Kim, Mari Turk, John Hardy, Eric M. Reiman, Andrew Saykin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Copy number variations (CNVs) are genomic regions that have added (duplications) or deleted (deletions) genetic material. They may overlap genes affecting their function and have been shown to be associated with disease. We previously investigated the role of CNVs in late-onset Alzheimer's disease (AD) and mild cognitive impairment using Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Institute of Aging-Late Onset AD/National Cell Repository for AD (NIA-LOAD/NCRAD) Family Study participants, and identified a number of genes overlapped by CNV calls. To confirm the findings and identify other potential candidate regions, we analyzed array data from a unique cohort of 1617 Caucasian participants (1022 AD cases and 595 controls) who were clinically characterized and whose diagnosis was neuropathologically verified. All DNA samples were extracted from brain tissue. CNV calls were generated and subjected to quality control (QC). 728 cases and 438 controls who passed all QC measures were included in case/control association analyses including candidate gene and genome-wide approaches. Rates of deletions and duplications did not significantly differ between cases and controls. Case-control association identified a number of previously reported regions (CHRFAM7A, RELN and DOPEY2) as well as a new gene (HLA-DRA). Meta-analysis of CHRFAM7A indicated a significant association of the gene with AD and/or MCI risk (P = 0.006, odds ratio = 3.986 (95% confidence interval 1.490-10.667)). A novel APP gene duplication was observed in one case sample. Further investigation of the identified genes in independent and larger samples is warranted.

Original languageEnglish
Article numbere50640
JournalPLoS One
Volume7
Issue number12
DOIs
StatePublished - Dec 5 2012

Fingerprint

Alzheimer disease
Alzheimer Disease
Genes
genes
Quality Control
quality control
HLA-DR alpha-Chains
Quality control
family studies
Gene Duplication
Gene Dosage
Genetic Association Studies
gene duplication
Neuroimaging
meta-analysis
sampling
odds ratio
Meta-Analysis
confidence interval
control methods

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Analysis of Copy Number Variation in Alzheimer's Disease in a Cohort of Clinically Characterized and Neuropathologically Verified Individuals. / Swaminathan, Shanker; Huentelman, Matthew J.; Corneveaux, Jason J.; Myers, Amanda J.; Faber, Kelley M.; Foroud, Tatiana; Mayeux, Richard; Shen, Li; Kim, Sungeun; Turk, Mari; Hardy, John; Reiman, Eric M.; Saykin, Andrew.

In: PLoS One, Vol. 7, No. 12, e50640, 05.12.2012.

Research output: Contribution to journalArticle

Swaminathan, S, Huentelman, MJ, Corneveaux, JJ, Myers, AJ, Faber, KM, Foroud, T, Mayeux, R, Shen, L, Kim, S, Turk, M, Hardy, J, Reiman, EM & Saykin, A 2012, 'Analysis of Copy Number Variation in Alzheimer's Disease in a Cohort of Clinically Characterized and Neuropathologically Verified Individuals', PLoS One, vol. 7, no. 12, e50640. https://doi.org/10.1371/journal.pone.0050640
Swaminathan, Shanker ; Huentelman, Matthew J. ; Corneveaux, Jason J. ; Myers, Amanda J. ; Faber, Kelley M. ; Foroud, Tatiana ; Mayeux, Richard ; Shen, Li ; Kim, Sungeun ; Turk, Mari ; Hardy, John ; Reiman, Eric M. ; Saykin, Andrew. / Analysis of Copy Number Variation in Alzheimer's Disease in a Cohort of Clinically Characterized and Neuropathologically Verified Individuals. In: PLoS One. 2012 ; Vol. 7, No. 12.
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