@article{4fb091bd5c274c058d0d7cf8eb3c1343,
title = "Application of systems biology approach identifies and validates GRB2 as a risk gene for schizophrenia in the Irish Case Control Study of Schizophrenia (ICCSS) sample",
abstract = "Recently, we prioritized 160 schizophrenia candidate genes (SZGenes) by integrating multiple lines of evidence and subsequently identified twenty-four pathways in which these 160 genes are overrepresented. Among them, four neurotransmitter-related pathways were top ranked. In this study, we extended our previous pathway analysis by applying a systems biology approach to identifying candidate genes for schizophrenia. We constructed protein-protein interaction subnetworks for four neurotransmitter-related pathways and merged them to obtain a general neurotransmitter network, from which five candidate genes stood out. We tested the association of four genes (GRB2, HSPA5, YWHAG, and YWHAZ) in the Irish Case-Control Study of Schizophrenia (ICCSS) sample (1021 cases and 626 controls). Interestingly, six of the seven tested SNPs in GRB2 showed significant signal, two of which (rs7207618 and rs9912608) remained significant after permutation test or Bonferroni correction, suggesting that GRB2 might be a risk gene for schizophrenia in Irish population. To our knowledge, this is the first report of GRB2 being significantly associated with schizophrenia in a specific population. Our results suggest that the systems biology approach is promising for identification of candidate genes and understanding the etiology of complex diseases.",
keywords = "Association, GRB2, GWAS, Neurotransmitter, Schizophrenia, Systems biology",
author = "Jingchun Sun and Chunling Wan and Peilin Jia and Fanous, {Ayman H.} and Kendler, {Kenneth S.} and Riley, {Brien P.} and Zhongming Zhao",
note = "Funding Information: We would like to thank Ms. Cuie Sun for her help in the genotyping, Mr. Tim B. Bigdeli and Drs. Xiangning Chen and Qi Chen for their help with the genotyping data analysis. The dataset(s) used for the analyses described in this manuscript were obtained from the database of Genotype and Phenotype (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number [GAIN: phs000021.v2.p1, nonGAIN: phs00167.v1.p1]. For GAIN dataset, the genotyping of samples was provided through the Genetic Association Information Network (GAIN). Samples and associated phenotype data for the Linking Genome-Wide Association Study of Schizophrenia were provided by P. German. The CATIE trial was funded by a grant from the National Institute of Mental Health ( N01 MH900001 ) along with MH074027 (PI PF Sullivan). Genotyping was funded by Eli Lilly and Company . The CATIE dataset was approved to use in this analysis through our application. Funding Information: This work was supported by the National Institutes of Health Grant Nos. AA017437 and MH083094, NARSAD Maltz Investigator Award to Z.Z., the Thomas F. and Kate Miller Jeffress Memorial Trust Fund grant No. J-900, and the Department of Psychiatry at the Vanderbilt University. The funding agencies had no further role in the design, implementation, or generation of this research report. ",
year = "2011",
month = feb,
doi = "10.1016/j.schres.2010.12.002",
language = "English (US)",
volume = "125",
pages = "201--208",
journal = "Schizophrenia Research",
issn = "0920-9964",
publisher = "Elsevier",
number = "2-3",
}