Secondary association of PDLIM5 with paranoid schizophrenia in Emirati patients

Schizophrenia is a clinically and genetically heterogeneous disorder of unknown etiology. PDLIM5 variants have been linked to schizophrenia and other related neuropsychiatric disorders and upregulated in the brain of schizophrenia patients suggesting a possible pathogenic role in disease progression. The aim of this study is to examine the potential association of schizophrenia in Emirati patients with previously reported variants in PDLIM5, PICK1, NRG3 or DISC1 genes. Consequently, we found a secondary association between PDLIM5 variants and the paranoid subtype of schizophrenia in Emirati Arabs suggesting that PDLIM5 may represent a determinate/marker for schizophrenia subtype specification. However, no associations were found with variants in PICK1, NRG3 or DISC1 genes.

[1]  L. Van Aelst,et al.  Rho GTPases, dendritic structure, and mental retardation. , 2005, Journal of neurobiology.

[2]  S. Tsai,et al.  Neuregulin 3 Genetic Variations and Susceptibility to Schizophrenia in a Chinese Population , 2008, Biological Psychiatry.

[3]  R. Hu Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) , 2003 .

[4]  J. Sebat,et al.  CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics , 2012, Cell.

[5]  J. D. Watson,et al.  708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits , 2013, Molecular Psychiatry.

[6]  J. Bourne,et al.  Do thin spines learn to be mushroom spines that remember? , 2007, Current Opinion in Neurobiology.

[7]  P. Visscher,et al.  Common polygenic variation contributes to risk of schizophrenia and bipolar disorder , 2009, Nature.

[8]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[9]  In English,et al.  The Numbers Count: Mental Disorders in America , 2013 .

[10]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[11]  C. Spencer,et al.  Biological Insights From 108 Schizophrenia-Associated Genetic Loci , 2014, Nature.

[12]  A. Bener,et al.  Does consanguinity increase the risk of schizophrenia? Study based on primary health care centre visits. , 2012, Mental health in family medicine.

[13]  Anders D. Børglum,et al.  Genome-wide association study identifies five new schizophrenia loci , 2011, Nature Genetics.

[14]  Simon C. Potter,et al.  Genome-wide Association Analysis Identifies 14 New Risk Loci for Schizophrenia , 2013, Nature Genetics.

[15]  P. Visscher,et al.  Rare chromosomal deletions and duplications increase risk of schizophrenia , 2008, Nature.

[16]  V. Eapen,et al.  Pathogenetic model for Tourette syndrome delineates overlap with related neurodevelopmental disorders including Autism , 2012, Translational Psychiatry.

[17]  Eden R Martin,et al.  Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders , 2014, Molecular Autism.

[18]  V. Eapen,et al.  Balance within the Neurexin Trans-Synaptic Connexus Stabilizes Behavioral Control , 2014, Front. Hum. Neurosci..

[19]  Jacques Fellay,et al.  WGAViewer: software for genomic annotation of whole genome association studies. , 2008, Genome research.

[20]  J. Bourne,et al.  Balancing structure and function at hippocampal dendritic spines. , 2008, Annual review of neuroscience.

[21]  A. McAllister Major Histocompatibility Complex I in Brain Development and Schizophrenia , 2014, Biological Psychiatry.

[22]  S. Levy,et al.  De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia , 2012, Nature Genetics.

[23]  M. Rietschel,et al.  The rate of consanguineous marriages among parents of schizophrenic patients in the Arab Bedouin population in Southern Israel , 2009, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[24]  D. Rujescu,et al.  Identification of new schizophrenia susceptibility loci in an ethnically homogeneous, family‐based, Arab‐Israeli sample , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[25]  Eric S. Lander,et al.  A polygenic burden of rare disruptive mutations in schizophrenia , 2014, Nature.

[26]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[27]  A. McAllister,et al.  MHCI negatively regulates synapse density during the establishment of cortical connections , 2011, Nature Neuroscience.

[28]  Patrick F Sullivan,et al.  The genomics of schizophrenia: update and implications. , 2013, The Journal of clinical investigation.

[29]  D. Pak,et al.  Postsynaptic PDLIM5/Enigma Homolog binds SPAR and causes dendritic spine shrinkage , 2010, Molecular and Cellular Neuroscience.

[30]  K. Iwamoto,et al.  Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders , 2004, Molecular Psychiatry.

[31]  Vishwajit L. Nimgaonkar,et al.  Consanguinity and increased risk for schizophrenia in Egypt , 2010, Schizophrenia Research.

[32]  D. Purpura,et al.  Dendritic Spine "Dysgenesis" and Mental Retardation , 1974, Science.

[33]  K. Dolić,et al.  Schizophrenia spectrum psychosis in a Croatian genetic isolate: genealogical reconstructions. , 2010, Psychiatria Danubina.

[34]  P. Patterson Immune involvement in schizophrenia and autism: Etiology, pathology and animal models , 2009, Behavioural Brain Research.

[35]  Stephan Ripke,et al.  Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs , 2012, Nature Genetics.

[36]  T. Petryshen,et al.  Genome-wide association studies of schizophrenia: does bigger lead to better results? , 2012, Current opinion in psychiatry.

[37]  L. Boulanger,et al.  MHC class I protein is expressed by neurons and neural progenitors in mid-gestation mouse brain , 2013, Molecular and Cellular Neuroscience.

[38]  M. Owen,et al.  Genetics of schizophrenia , 2005, Current Opinion in Behavioral Sciences.

[39]  M. Itokawa,et al.  A Polymorphism in the PDLIM5 Gene Associated with Gene Expression and Schizophrenia , 2006, Biological Psychiatry.

[40]  M. King,et al.  Schizophrenia: a common disease caused by multiple rare alleles , 2007, British Journal of Psychiatry.