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.
Keywords: Alzheimer's disease, association study, CHRFAM7A, copy number variation, dementia, IMMP2L, NIALOAD/ NCRAD, replication.
Current Alzheimer Research
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/156720512802455331 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Recent Progress in Pharmacological and Non-Pharmacological Treatment Options of Major Depression
Current Pharmaceutical Design Nanoparticle-Encapsulated Bryostatin-1 Activates α-Secretase and PKC Isoforms In vitro and Facilitates Acquisition and Retention of Spatial Learning in an Alzheimer's Disease Mouse Model
Current Alzheimer Research Dual Functional Small Molecule Probes as Fluorophore and Ligand for Misfolding Proteins
Current Organic Chemistry Stress, Depression, Resilience and Ageing: A Role for the LPA-LPA1 Pathway
Current Neuropharmacology Inhibition of microRNA-155 Alleviates Cognitive Impairment in Alzheimer’s Disease and Involvement of Neuroinflammation
Current Alzheimer Research Nanotechnology Based Diagnostic and Therapeutic Strategies for Neuroscience with Special Emphasis on Ischemic Stroke
Current Medicinal Chemistry Genetic Variations in CHRNA7 or CHRFAM7 and Susceptibility to Dementia
Current Drug Targets Memantine: A Therapeutic Approach in Treating Alzheimers and Vascular Dementia
Current Drug Targets - CNS & Neurological Disorders Ageing as a Trait de Union Between Diabetes and Dementia for Frailty
CNS & Neurological Disorders - Drug Targets Nanomedicines for Brain Targeting: A Patent Review
Recent Patents on Nanomedicine The Role of HIV-1 DNA as an Additional Marker of HIV-1 Infection
Current HIV Research Targeting Neurotrophin Receptors in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Biomarkers of Alzheimer’s Disease: An Overview of the Recent Inventions
Recent Patents on Biomarkers Influenza and Stroke Risk: A Key Target Not to be Missed?
Infectious Disorders - Drug Targets Metabolic Dysfunction in Alzheimers Disease and Related Neurodegenerative Disorders
Current Alzheimer Research Neuroprotective and Neurotoxic Implications of α7 Nicotinic Acetylcholine Receptor and Aβ Interaction: Therapeutic Options in Alzheimer's Disease
Current Drug Targets The Genetic Variation of ARRB2 is Associated with Late-onset Alzheimer's Disease in Han Chinese
Current Alzheimer Research Dopamine Neurotransmission and Atypical Antipsychotics in Prefrontal Cortex: A Critical Review
Current Topics in Medicinal Chemistry Vitamin D Increases Aβ140 Plasma Levels and Protects Lymphocytes from Oxidative Death in Mild Cognitive Impairment Patients
Current Alzheimer Research Therapeutic Hypothermia in Brain Injuries and Related Diseases
Recent Patents on Inflammation & Allergy Drug Discovery