Convergent genomic studies identify association of GRIK2 and NPAS2 with chronic fatigue syndrome.
Neuropsychobiology
; 64(4): 183-94, 2011.
Article
in En
| MEDLINE
| ID: mdl-21912186
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Fatigue Syndrome, Chronic
/
Receptors, Kainic Acid
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Genetic Predisposition to Disease
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Basic Helix-Loop-Helix Transcription Factors
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Nerve Tissue Proteins
Type of study:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
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Male
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Middle aged
Language:
En
Journal:
Neuropsychobiology
Year:
2011
Type:
Article
Affiliation country:
United States