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PMID: 22486522 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Analysis of copy number variation in Alzheimer's disease: the NIALOAD/ NCRAD Family Study.

Current Alzheimer research ·Vol. 9 ·No. 7 ·2012-09-00 ·Pages 801-14

Swaminathan S, Shen L, Kim S, Inlow M, West JD, Faber KM, Foroud T, Mayeux R, Saykin AJ, Alzheimer's Disease Neuroimaging Initiative, NIA-LOAD/NCRAD Family Study Group

Abstract

Copy number variants (CNVs) are DNA regions that have gains (duplications) or losses (deletions) of genetic material. CNVs may encompass a single gene or multiple genes and can affect their function. They are hypothesized to play an important role in certain diseases. We previously examined the role of CNVs in late-onset Alzheimer's disease (AD) and mild cognitive impairment (MCI) using participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study and identified gene regions overlapped by CNVs only in cases (AD and/or MCI) but not in controls. Using a similar approach as ADNI, we investigated the role of CNVs using 794 AD and 196 neurologically evaluated control non-Hispanic Caucasian NIA-LOAD/NCRAD Family Study participants with DNA derived from blood/brain tissue. The controls had no family history of AD and were unrelated to AD participants. CNV calls were generated and analyzed after detailed quality review. 711 AD cases and 171 controls who passed all quality thresholds were included in case/control association analyses, focusing on candidate gene and genome-wide approaches. We identified genes overlapped by CNV calls only in AD cases but not controls. A trend for lower CNV call rate was observed for deletions as well as duplications in cases compared to controls. Gene-based association analyses confirmed previous findings in the ADNI study (ATXN1, HLA-DPB1, RELN, DOPEY2, GSTT1, CHRFAM7A, ERBB4, NRXN1) and identified a new gene (IMMP2L) that may play a role in AD susceptibility. Replication in independent samples as well as further analyses of these gene regions is warranted.

MeSH Terms
Aged Aged, 80 and over Alzheimer Disease/genetics Apolipoproteins E/genetics Case-Control Studies Cognitive Dysfunction/genetics DNA Copy Number Variations Female Gene Dosage Genetic Predisposition to Disease Genome-Wide Association Study Genotype Humans Male Polymorphism, Single Nucleotide Reelin Protein Whites/genetics
Chemicals
Apolipoproteins E Reelin Protein RELN protein, human
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Swaminathan Shanker
Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA.
Shen Li
Kim Sungeun
Inlow Mark
West John D
Faber Kelley M
Foroud Tatiana
Mayeux Richard
Saykin Andrew J
Alzheimer's Disease Neuroimaging Initiative
NIA-LOAD/NCRAD Family Study Group
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Article Info
Journal
Current Alzheimer research
Abbr.
Curr Alzheimer Res
ISSN
1875-5828
DOI
10.2174/156720512802455331
Published
2012-09-00
Pages
801-14
Language
English
Region
United Arab Emirates
NLM ID
101208441
PMCID
PMC3500615
Subset
IM
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PubMed source DOI: 10.2174/156720512802455331 PMC Full Text View journal details
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