Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.

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 dise...

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Autores principales:	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 J Saykin, Alzheimer's Disease Neuroimaging Initiative and NIA-LOAD/NCRAD Family Study Group
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3c5684af656b4abeb7c5e3c3fea08753
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spelling	oai:doaj.org-article:3c5684af656b4abeb7c5e3c3fea087532021-11-18T08:06:23ZAnalysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.1932-620310.1371/journal.pone.0050640https://doaj.org/article/3c5684af656b4abeb7c5e3c3fea087532012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23227193/?tool=EBIhttps://doaj.org/toc/1932-6203Copy 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.Shanker SwaminathanMatthew J HuentelmanJason J CorneveauxAmanda J MyersKelley M FaberTatiana ForoudRichard MayeuxLi ShenSungeun KimMari TurkJohn HardyEric M ReimanAndrew J SaykinAlzheimer's Disease Neuroimaging Initiative and NIA-LOAD/NCRAD Family Study GroupPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e50640 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 J Saykin Alzheimer's Disease Neuroimaging Initiative and NIA-LOAD/NCRAD Family Study Group Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
description	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.
format	article
author	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 J Saykin Alzheimer's Disease Neuroimaging Initiative and NIA-LOAD/NCRAD Family Study Group
author_facet	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 J Saykin Alzheimer's Disease Neuroimaging Initiative and NIA-LOAD/NCRAD Family Study Group
author_sort	Shanker Swaminathan
title	Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
title_short	Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
title_full	Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
title_fullStr	Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
title_full_unstemmed	Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
title_sort	analysis of copy number variation in alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3c5684af656b4abeb7c5e3c3fea08753
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Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.

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