Data analysis code for the paper:
Genetic and environmental regulation of caudate nucleus transcriptome in schizophrenia
Authors: Kynon JM Benjamin1-3, Arthur S Feltrin4, André Rocha Barbosa1,5,6, Andrew E Jaffe1,2,7-10, Joshua M Stolz1, Leonardo Collado-Torres1,11, Louise A Huuki1, Qiang Chen1, Emily E Burke1, Ria Arora1, Joo Heon Shin1, William S Ulrich1, Amy Deep-Soboslay1, Ran Tao1, the BrainSeq Consortium, Thomas M Hyde1,3,7, Joel E Kleinman1,2, Jennifer A Erwin1-3,7*, Daniel R Weinberger1-3,7,8*, Apuã CM Paquola1,3*
1Lieber Institute for Brain Development, Baltimore, MD, USA
2Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA
3Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
4Center for Mathematics, Computation and Cognition, Federal University of ABC, Santo André, SP, Brazil
5Inter-institutional Graduate Program on Bioinformatics, University of São Paulo, São Paulo, SP, Brazil
6Institute of Mathematics and Statistics, University of São Paulo, São Paulo, SP, Brazil
7Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
8McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
9Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
10Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
11Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA
*Correspondence to: apua.paquola@libd.org, drweinberger@libd.org, jennifer.erwin@libd.org
Recent studies of gene expression in the human brain have provided biological insights about the genetic origins of psychiatric disorders, such as schizophrenia. Most of these studies, however, have focused exclusively on cortical regions though subcortical nuclei, such as striatum, have figured prominently in the circuitry implicated in schizophrenia and its dense dopaminergic innervation is targeted by current antipsychotic drugs. To gain novel insight into risk mechanisms underlying schizophrenia, we performed a comprehensive analysis of the genetic and transcriptional landscape of schizophrenia in the postmortem caudate nucleus of 443 individuals. Integrating expression quantitative trait loci (eQTLs) analysis, Mendelian Randomization with the latest schizophrenia GWAS, transcriptome wide association study (TWAS), and differential expression analysis, we identified many new genes associated with schizophrenia risk including possibly the dopamine D2 receptor short isoform. We examined the effect of antipsychotics in the caudate and show extensive influence on gene expression. Using a new approach based on deep neural networks, we construct caudate nucleus gene expression networks that highlight interactions involving schizophrenia risk. Altogether, these analyses provide a new resource for the study of schizophrenia that can bring insight into risk mechanisms and potential novel therapeutic targets.
Processed data and eQTL Browswer can be found here: http://erwinpaquolalab.libd.org/caudate_eqtl/