Analysis of Copy Number Variation in Alzheimer’s Disease: The NIALOAD/ NCRAD Family Study

Title:Analysis of Copy Number Variation in Alzheimer’s Disease: The NIALOAD/ NCRAD Family Study

Volume: 9 Issue: 7

Author(s): Shanker Swaminathan, Li Shen, Sungeun Kim, Mark Inlow, John D. West, Kelley M. Faber, Tatiana Foroud, Richard Mayeux and Andrew J. Saykin

Affiliation:

Keywords: Alzheimer's disease, association study, CHRFAM7A, copy number variation, dementia, IMMP2L, NIALOAD/ NCRAD, replication.

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.

Cite this article as:

Swaminathan Shanker, Shen Li, Kim Sungeun, Inlow Mark, D. West John, M. Faber Kelley, Foroud Tatiana, Mayeux Richard and J. Saykin Andrew, Analysis of Copy Number Variation in Alzheimer’s Disease: The NIALOAD/ NCRAD Family Study, Current Alzheimer Research 2012; 9 (7) . https://dx.doi.org/10.2174/156720512802455331