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Table of Contents
Vol. 64, No. 4, 2011
Issue release date: September 2011
Section title: Original Paper
Free Access
Neuropsychobiology 2011;64:183–194

Convergent Genomic Studies Identify Association of GRIK2 and NPAS2 with Chronic Fatigue Syndrome

Smith A.K.a, 1 · Fang H.b · Whistler T.a · Unger E.R.a · Rajeevan M.S.a
aDivision of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Ga., and bZ-Tech Corporation, an ICF International Company at NCTR/Food and Drug Administration, Jefferson, Ark., USA
email Corresponding Author

Mangalathu S. Rajeevan

Division of High-Consequence Pathogens and Pathology

Centers for Disease Control and Prevention, 1600 Clifton Road

Atlanta, GA 30333 (USA)

Tel. +1 404 639 2931, E-Mail mor4@cdc.gov

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Background: There is no consistent evidence of specific gene(s) or molecular pathways that contribute to the pathogenesis, therapeutic intervention or diagnosis of chronic fatigue syndrome (CFS). While multiple studies support a role for genetic variation in CFS, genome-wide efforts to identify associated loci remain unexplored. We employed a novel convergent functional genomics approach that incorporates the findings from single-nucleotide polymorphism (SNP) and mRNA expression studies to identify associations between CFS and novel candidate genes for further investigation. Methods: We evaluated 116,204 SNPs in 40 CFS and 40 nonfatigued control subjects along with mRNA expression of 20,160 genes in a subset of these subjects (35 CFS subjects and 27 controls) derived from a population-based study. Results: Sixty-five SNPs were nominally associated with CFS (p < 0.001), and 165 genes were differentially expressed (≧4-fold; p ≤ 0.05) in peripheral blood mononuclear cells of CFS subjects. Two genes, glutamate receptor, ionotropic, kinase 2 (GRIK2) and neuronal PAS domain protein 2 (NPAS2), were identified by both SNP and gene expression analyses. Subjects with the G allele of rs2247215 (GRIK2) were more likely to have CFS (p = 0.0005), and CFS subjects showed decreased GRIK2 expression (10-fold; p = 0.015). Subjects with the T allele of rs356653 (NPAS2) were more likely to have CFS (p = 0.0007), and NPAS2 expression was increased (10-fold; p = 0.027) in those with CFS. Conclusion: Using an integrated genomic strategy, this study suggests a possible role for genes involved in glutamatergic neurotransmission and circadian rhythm in CFS and supports further study of novel candidate genes in independent populations of CFS subjects.

© 2011 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: August 26, 2010
Accepted: February 21, 2011
Published online: September 09, 2011
Issue release date: September 2011

Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 2

ISSN: 0302-282X (Print)
eISSN: 1423-0224 (Online)

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