Olfactory copy number association with age at onset of Alzheimer disease
Citation Manager Formats
Make Comment
See Comments
This article has a correction. Please see:

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objectives: Copy number variants (CNVs) have been recognized as a source of genetic variation that contributes to disease phenotypes. Alzheimer disease (AD) has high heritability for occurrence and age at onset (AAO). We performed a cases-only genome-wide CNV association study for age at onset of AD.
Methods: The discovery case series (n = 40 subjects with AD) was evaluated using array comparative genome hybridization (aCGH). A replication case series (n = 507 subjects with AD) was evaluated using Affymetrix array (n = 243) and multiplex ligation-dependent probe amplification (n = 264). Hazard models related onset age to CNV.
Results: The discovery sample identified a chromosomal segment on 14q11.2 (19.3–19.5 Mb, NCBI build 36, UCSC hg18 March 2006) as a region of interest (genome-wide adjusted p = 0.032) for association with AAO of AD. This region encompasses a cluster of olfactory receptors. The replication sample confirmed the association (p = 0.035). The association was found for each APOE4 gene dosage (0, 1, and 2).
Conclusion: High copy number in the olfactory receptor region on 14q11.2 is associated with younger age at onset of AD.
Footnotes
-
Study funding: Supported by Baylor College of Medicine through start-up funds to the PI. The Affymetrix dataset was provided to the PI from the Texas Alzheimer Research Consortium funded by the State of Texas. The funders have no role in the study.
-
Supplemental data at www.neurology.org
-
- AAO
- age at onset
- aCGH
- array comparative genome hybridization
- AD
- Alzheimer disease
- CI
- confidence interval
- CN
- copy number
- CNV
- copy number variant
- DZ
- dizygotic
- FISH
- fluorescent in situ hybridization
- HR
- hazard ratio
- LD
- linkage disequilibrium
- MLPA
- multiplex ligation-dependent probe amplification
- MZ
- monozygotic
- OR
- odds ratio
- RR
- relative risk
- SNP
- single nucleotide polymorphism.
- Received July 20, 2010.
- Accepted December 22, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. David E. Vaillancourt and Dr. Shannon Y. Chiu
► Watch
Topics Discussed
Alert Me
Recommended articles
-
Articles
Role of common and rare APP DNA sequence variants in Alzheimer diseaseB.V. Hooli, G. Mohapatra, M. Mattheisen et al.Neurology, April 04, 2012 -
Abstracts
19th Workshop of the International Stroke Genetics Consortium, April 28–29, 2016, Boston, Massachusetts, USAet al.Neurology: Genetics, March 30, 2017 -
Article
Exome-chip association analysis of intracranial aneurysmsFemke N.G. van 't Hof, Dongbing Lai, Jessica van Setten et al.Neurology, November 15, 2019 -
Views & Reviews
Late-onset vs nonmendelian early-onset Alzheimer diseaseA distinction without a difference?Christiane Reitz, Ekaterina Rogaeva, Gary W. Beecham et al.Neurology: Genetics, October 06, 2020