Wednesday, November 3, 2010

D. Mehta: Polymorphisms in FKBPS define biologically distinct subtypes of PTSD #ASHG2010 notes

Divya Mehta  et al
Polymorphisms in FKBPS define biologically distinct subtypes of PTSD: evidence from endocrine and gene expression studies

Individuals with PTSD have supersensitive GR.
FKBP5 is a cochaperone, part of a mature heteroGR complex, and regulator of the heteroGR complex.
FKBP5 SNPs interact with child abuse to predict PTSD symptoms. 
Binder et al. 2008; Yehuda group paper.

African American sample from suburban Atlanta.
218 participants with trauma history.
PSS (PTSD measure)
183 transcripts associated with trauma scores, none previously described.
Then they stratified transcript results by genotype*PTSD --significant interaction, no main effect.
32 significant interactions, transcripts previously identified, associated with PTSD symptoms X FKBP5 SNP rs 92950158.
Opposite effects of transcripts in carriers of risk and protective markers.

Complmented with a literature based - pathway mining approach. 
Use intermediate phenotypes.
use co-expression networks.

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