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Support for involvement of neuregulin 1 in schizophrenia pathophysiology
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Journal Article
Support for involvement of neuregulin 1 in schizophrenia pathophysiology
2005
Overview
Schizophrenia is a common, multigenic psychiatric disorder. Linkage studies, including a recent meta-analysis of genome scans, have repeatedly implicated chromosome 8p12-p23.1 in schizophrenia susceptibility. More recently, significant association with a candidate gene on 8p12, neuregulin 1 (
NRG1
), has been reported in several European and Chinese samples. We investigated
NRG1
for association in schizophrenia patients of Portuguese descent to determine whether this gene is a risk factor in this population. We tested
NRG1
markers and haplotypes for association in 111 parent-proband trios, 321 unrelated cases, and 242 control individuals. Associations were found with a haplotype that overlaps the risk haplotype originally reported in the Icelandic population (‘Hap
ICE
’), and two haplotypes located in the 3′ end of
NRG1
(all
P
<0.05). However, association was not detected with Hap
ICE
itself. Comparison of NRG1 transcript expression in peripheral leukocytes from schizophrenia patients and unaffected siblings identified 3.8-fold higher levels of the SMDF variant in patients (
P=
0.039). Significant positive correlations (
P
<0.001) were found between SMDF and HRG-beta 2 expression and between HRG-gamma and ndf43 expression, suggesting common transcriptional regulation of NRG1 variants. In summary, our results suggest that haplotypes across
NRG1
and multiple NRG1 variants are involved in schizophrenia.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Chromosomes, Human, Pair 8 - genetics
/ European Continental Ancestry Group - genetics
/ Family
/ Female
/ Genetic Predisposition to Disease - ethnology
/ Genomes
/ Genomics
/ Humans
/ Male
/ Medicine
/ Microsatellite Repeats - genetics
/ Nerve Tissue Proteins - genetics
/ Pedigree
