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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Nogo receptor 1 (RTN4R) as a candidate gene for schizophrenia: Analysis using human and mouse genetic approaches
PLoS ONE, Volume 2, No. 11, Article e1234, Year 2007
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Description
Background. NOGO Receptor 1 (RTN4R) regulates axonal growth, as well as axort regeneration after injury. The gene maps to the 22q11.2 schizophrenia susceptibility locus and is thus a strong functional and positional candidate gene. Methodology/Principal Findings. We evaluate evidence for genetic association between common RTN4R polymorphisms and schizophrenia in a large family sample of Afrikaner origin and screen the exonic sequence of RTN4R for rare variants in an independent sample from the U.S. We also employ animal model studies to assay a panel of schizophrenia-related behavioral tasks in an Rtn4r-deficient mouse model. We found weak sex-specific evidence for association between common RTN4R polymorphisms and schizophrenia in the Afrikaner patients. In the U.S. sample, we identified two novel non-conservative RTN4R coding variants in two patients with schizophrenia that were absent in 600 control chromosomes. In our complementary mouse model studies, we identified a haploinsufficient effect of Rtn4r on locomotor activity, but normal performance in schizophrenia-related behavioral tasks. We also provide evidence that Rtn4r deficiency can modulate the long-term behavioral effects of transient postnatal N-methyl-D-aspartate (NMDA) receptor hypofunction. Conclusions. Our results do not support a major role of RTN4R in susceptibility to schizophrenia or the cognitive and behavioral deficits observed in individuals with 22q11 microdeletions. However, they suggest that RTN4R may modulate the genetic risk or clinical expression of schizophrenia in a subset of patients and identify additional studies that will be necessary to clarify the role of RTN4R in psychiatric phenotypes. In addition, our results raise interesting issues about evaluating the significance of rare genetic variants in disease and their role in causation. © 2007 Hsu et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2077930/bin/pone.0001234.s001.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2077930/bin/pone.0001234.s002.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2077930/bin/pone.0001234.s003.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2077930/bin/pone.0001234.s004.tif
Authors & Co-Authors
Hsu, Ruby
United States, New York
Columbia University
Woodroffe, Abigail
United States, Ann Arbor
University of Michigan, Ann Arbor
Lai, Wen Sung
United States, New York
Vagelos College of Physicians and Surgeons
Cook, Melloni N.
United States, Memphis
University of Memphis
Mukai, Jun
United States, New York
Vagelos College of Physicians and Surgeons
Dunning, Jonathan P.
United States, Memphis
University of Memphis
Swanson, Douglas James
United States, Memphis
University of Tennessee Health Science Center
Roos, J. L.
South Africa, Pretoria
University of Pretoria
Abecasis, Gonçalo R.
United States, Ann Arbor
University of Michigan, Ann Arbor
Karayiorgou, Maria
United States, New York
Vagelos College of Physicians and Surgeons
Gogos, Joseph A.
United States, New York
Columbia University
United States, New York
Vagelos College of Physicians and Surgeons
Statistics
Citations: 81
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0001234
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Maternal And Child Health
Mental Health
Violence And Injury