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PMID: 21569597 Published · epublish English Journal Article

Gene expression endophenotypes: a novel approach for gene discovery in Alzheimer's disease.

Molecular neurodegeneration ·Vol. 6 ·2011-05-14 ·Pages 31

Ertekin-Taner N

Abstract

Uncovering the underlying genetic component of any disease is key to the understanding of its pathophysiology and may open new avenues for development of therapeutic strategies and biomarkers. In the past several years, there has been an explosion of genome-wide association studies (GWAS) resulting in the discovery of novel candidate genes conferring risk for complex diseases, including neurodegenerative diseases. Despite this success, there still remains a substantial genetic component for many complex traits and conditions that is unexplained by the GWAS findings. Additionally, in many cases, the mechanism of action of the newly discovered disease risk variants is not inherently obvious. Furthermore, a genetic region with multiple genes may be identified via GWAS, making it difficult to discern the true disease risk gene. Several alternative approaches are proposed to overcome these potential shortcomings of GWAS, including the use of quantitative, biologically relevant phenotypes. Gene expression levels represent an important class of endophenotypes. Genetic linkage and association studies that utilize gene expression levels as endophenotypes determined that the expression levels of many genes are under genetic influence. This led to the postulate that there may exist many genetic variants that confer disease risk via modifying gene expression levels. Results from the handful of genetic studies which assess gene expression level endophenotypes in conjunction with disease risk suggest that this combined phenotype approach may both increase the power for gene discovery and lead to an enhanced understanding of their mode of action. This review summarizes the evidence in support of gene expression levels as promising endophenotypes in the discovery and characterization of novel candidate genes for complex diseases, which may also represent a novel approach in the genetic studies of Alzheimer's and other neurodegenerative diseases.

Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Ertekin-Taner Nilüfer
Mayo Clinic Florida, Departments of Neurology and Neuroscience, 4500 San Pablo Road, Birdsall 210, Jacksonville, Florida 32224 USA. taner.nilufer@mayo.edu.
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Article Info
Journal
Molecular neurodegeneration
Abbr.
Mol Neurodegener
ISSN
1750-1326
DOI
10.1186/1750-1326-6-31
Email
taner.nilufer@mayo.edu
Published
2011-05-14
Epub
2011-00-14
Pages
31
Language
English
Region
England
NLM ID
101266600
PMCID
PMC3113300
Grants
NIA NIH HHS · P50 AG016574 · United States
NIA NIH HHS · R01 AG032990 · United States
External Links
PubMed source DOI: 10.1186/1750-1326-6-31 PMC Full Text View journal details
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