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file download- http://www.mediafire.com/?lkczr4brmbw9jsb
Convergent Genomic Studies Identify Association of GRIK2 and NPAS2
with Chronic Fatigue Syndrome
Alicia K. Smith, Hong Fang, Toni Whistler, Elizabeth R. Unger,
Mangalathu S. Rajeevan
Neuropsychobiology 2011;64:183=96194 DOI: 10.1159/000326692
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 ( 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 =3D 0.0005), and CFS subjects showed
decreased GRIK2 expression (10-fold; p =3D 0.015). Subjects with the T
allele of rs356653 (NPAS2) were more likely to have CFS (p =3D 0.0007),
and NPAS2 expression was increased (10-fold; p =3D 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.
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