@article{52bb258b56bd4e75a371a575622dd8ce,
title = "Transcriptome sequencing study implicates immune-related genes differentially expressed in schizophrenia: New data and a meta-analysis",
abstract = "We undertook an RNA sequencing (RNAseq)-based transcriptomic profiling study on lymphoblastoid cell lines of a European ancestry sample of 529 schizophrenia cases and 660 controls, and found 1058 genes to be differentially expressed by affection status. These differentially expressed genes were enriched for involvement in immunity, especially the 697 genes with higher expression in cases. Comparing the current RNAseq transcriptomic profiling to our previous findings in an array-based study of 268 schizophrenia cases and 446 controls showed a highly significant positive correlation over all genes. Fifteen (18%) of the 84 genes with significant (false discovery rate <.05) expression differences between cases and controls in the previous study and analyzed here again were differentially expressed by affection status here at a genome-wide significance level (Bonferroni Po<.05 adjusted for 8141 analyzed genes in total, or P< ∼ 6.1 × 10-6), all with the same direction of effect, thus providing corroborative evidence despite each sample of fully independent subjects being studied by different technological approaches. Meta-analysis of the RNAseq and array data sets (797 cases and 1106 controls) showed 169 additional genes (besides those found in the primary RNAseq-based analysis) to be differentially expressed, and provided further evidence of immune gene enrichment. In addition to strengthening our previous array-based gene expression differences in schizophrenia cases versus controls and providing transcriptomic support for some genes implicated by other approaches for schizophrenia, our study detected new genes differentially expressed in schizophrenia. We highlight RNAseq-based differential expression of various genes involved in neurodevelopment and/or neuronal function, and discuss caveats of the approach.",
author = "Sanders, {A. R.} and Drigalenko, {E. I.} and J. Duan and W. Moy and J. Freda and G{\"o}ring, {H. H.H.} and Gejman, {P. V.} and Levinson, {D. F.} and J. Shi and Buccola, {N. G.} and Mowry, {B. J.} and R. Freedman and A. Olincy and F. Amin and Black, {D. W.} and Silverman, {J. M.} and Byerley, {W. F.} and Cloninger, {C. R.} and Svrakic, {D. M.}",
note = "Funding Information: We thank the GAIN quality control team (GR Abecasis and J Paschall) for making important contributions to the project; S Purcell for assistance with PLINK; personnel at Rutgers University Cell and DNA Repository (JA Tischfield and DA Fugman) for advice and assistance with the LCLs; D He at NorthShore University HealthSystem for technical assistance; T Lehner and G Senthil at the National Institute of Mental Health for their support and scientific advice; MGS, which includes PV Gejman, AR Sanders, J Duan (NorthShore University HealthSystem, and University of Chicago, IL, USA), DF Levinson (Stanford University, CA, USA), J Shi (National Cancer Institute, MD, USA), NG Buccola (Louisiana State University Health Sciences Center, LA, USA), BJ Mowry (Queensland Centre for Mental Health Research, Brisbane and Queensland Brain Institute, The University of Queensland, Australia), R Freedman, A Olincy (University of Colorado Denver, CO, USA), F Amin (Atlanta Veterans Affairs Medical Center and Emory University, GA, USA), DW Black (University of Iowa Carver College of Medicine, IA, USA), JM Silverman (Icahn School of Medicine at Mount Sinai, NY, USA), WF Byerley (University of California at San Francisco, CA, USA), CR Cloninger, DM Svrakic (Washington University, MO, USA); and the study participants and the research staff at the study sites. This work was supported primarily by the National Institutes of Health (NIH grants RC2MH090030 to ARS, R01MH094116 to HHHG and R01MH094091 to PVG); as well as for MGS by NIH grants (R01MH067257 to NGB, R01MH059588 to BJM, R01MH059571 to PVG, R01MH059565 to RF, R01MH059587 to FA, R01MH060870 to WFB, R01MH059566 to DWB, R01MH059586 to JMS, R01MH061675 to DFL, R01MH060879 to CRC, R01MH081800 to PVG, U01MH046276 to CRC, U01MH046289 to C Kaufmann, U01MH046318 to MT Tsuang, U01MH079469 to PVG and U01MH079470 to DFL), the Genetic Association Information Network (GAIN, for genotyping of half of the European ancestry sample and almost all the African American sample) and The Paul Michael Donovan Charitable Foundation. Genotyping was carried out by the Center for Genotyping and Analysis at the Broad Institute of Harvard and MIT (SG and DBM) is supported by NIH grant U54RR020278. Analyses done in San Antonio (EID and HHHG) were conducted in facilities constructed with support from NIH grant RR017515 and a gift from the AT&T Foundation.",
year = "2017",
doi = "10.1038/tp.2017.47",
language = "English (US)",
volume = "7",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "4",
}