CDC study may link expression of two genes to CFS: Relate to learning/memory and sleep-wake cycle

Article:
Convergent Genomic Studies Identify Association of GRIK2 and NPAS2 with Chronic Fatigue Syndrome
– Source: Neuropsychobiology, Sep 9, 2011

By Alicia K Smith, et al.

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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 ( 6 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 [important for learning and memory] and circadian rhythm [wake sleep cycle] in CFS

• And supports further study of novel candidate genes in independent populations of CFS subjects.

Source: Neuropsychobiology, Sep 9, 2011. 64:183–194. DOI: 10.1159/000326692, by Smith AK, Fang H, Whistler T, Unger ER, Rajeevan MS. Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia; Z-Tech Corporation, an ICF International Company at NCTR/Food and Drug Administration, Jefferson, Arkansas, USA.

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