Gene discovery through imaging genetics : identification of two novel genes associated with schizophrenia
Articolo
Data di Pubblicazione:
2009
Citazione:
Gene discovery through imaging genetics : identification of two novel genes associated with schizophrenia / S.G. Potkin, J.A. Turner, J.A. Fallon, A. Lakatos, D.B. Keator, G. Guffanti, F. Macciardi, FBIRN. - In: MOLECULAR PSYCHIATRY. - ISSN 1359-4184. - 14:4(2009), pp. 416-428.
Abstract:
We have discovered two genes, RSRC1 and ARHGAP18, associated with schizophrenia and in
an independent study provided additional support for this association. We have both
discovered and verified the association of two genes, RSRC1 and ARHGAP18, with
schizophrenia. We combined a genome-wide screening strategy with neuroimaging measures
as the quantitative phenotype and identified the single nucleotide polymorphisms (SNPs)
related to these genes as consistently associated with the phenotypic variation. To control for
the risk of false positives, the empirical P-value for association significance was calculated
using permutation testing. The quantitative phenotype was Blood-Oxygen-Level Dependent
(BOLD) Contrast activation in the left dorsal lateral prefrontal cortex measured during a working
memory task. The differential distribution of SNPs associated with these two genes in cases
and controls was then corroborated in a larger, independent sample of patients with
schizophrenia (n = 82) and healthy controls (n = 91), thus suggesting a putative etiological
function for both genes in schizophrenia. Up until now these genes have not been linked to any
neuropsychiatric illness, although both genes have a function in prenatal brain development.
We introduce the use of functional magnetic resonance imaging activation as a quantitative phenotype in conjunction with genome-wide association as a gene discovery tool.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
cognition ; fMRI ; GWAS ; case–control study ; quantitative trait loci ; prefrontal cortex
Elenco autori:
S.G. Potkin, J.A. Turner, J.A. Fallon, A. Lakatos, D.B. Keator, G. Guffanti, F. Macciardi, FBIRN
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