Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
A genome-wide association study identifies a gene network associated with paranoid schizophrenia and antipsychotics-induced tardive dyskinesia. / Levchenko, Anastasia ; Kanapin, Alexander ; Samsonova, Anastasia ; Fedorenko, Olga Yu.; Kornetova, Elena G. ; Nurgaliev, Timur ; Mazo, Galina E.; Semke, Arkadiy V.; Kibitov, Alexander O. ; Bokhan, Nikolay A.; Gainetdinov, Raul R. ; Ivanova, Svetlana A.
в: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Том 105, 110134, 01.03.2021.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
}
TY - JOUR
T1 - A genome-wide association study identifies a gene network associated with paranoid schizophrenia and antipsychotics-induced tardive dyskinesia
AU - Levchenko, Anastasia
AU - Kanapin, Alexander
AU - Samsonova, Anastasia
AU - Fedorenko, Olga Yu.
AU - Kornetova, Elena G.
AU - Nurgaliev, Timur
AU - Mazo, Galina E.
AU - Semke, Arkadiy V.
AU - Kibitov, Alexander O.
AU - Bokhan, Nikolay A.
AU - Gainetdinov, Raul R.
AU - Ivanova, Svetlana A.
N1 - Funding Information: This work was supported by the Russian Science Foundation [grant number 19-75-30008 ]. Funding Information: The authors thank Dr. Anton J.M. Loonen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands, for the clinician training that he organized and conducted at the Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia. Dr. Anton J.M. Loonen is a leading expert in clinical aspects of TD (Loonen, Doorschot, 2000, 2001, Loonen and van Praag, 2007). Anastasia Levchenko, Timur Nurgaliev, and Raul R. Gainetdinov were supported by funding for the project # 51143531 from Saint Petersburg State University , Saint Petersburg, Russia. In addition, Alexander Kanapin and Anastasia Samsonova were supported by funding for the project # 51148284 from Saint Petersburg State University , Saint Petersburg, Russia. This work was carried out within the framework of the Tomsk Polytechnic University Competitiveness Enhancement Program and as part of the Russian National Consortium for Psychiatric Genetics (RNCPG) ( Fedorenko et al., 2019 ).
PY - 2021/3/1
Y1 - 2021/3/1
N2 - In the present study we conducted a genome-wide association study (GWAS) in a cohort of 505 patients with paranoid schizophrenia (SCZ), of which 95 had tardive dyskinesia (TD), and 503 healthy controls. Using data generated by the PsychENCODE Consortium (PEC) and other bioinformatic databases, we revealed a gene network, implicated in neurodevelopment and brain function, associated with both these disorders. Almost all these genes are in gene or isoform co-expression PEC network modules important for the functioning of the brain; the activity of these networks is also altered in SCZ, bipolar disorder and autism spectrum disorders. The associated PEC network modules are enriched for gene ontology terms relevant to the brain development and function (CNS development, neuron development, axon ensheathment, synapse, synaptic vesicle cycle, and signaling receptor activity) and to the immune system (inflammatory response). Results of the present study suggest that orofacial and limbtruncal types of TD seem to share the molecular network with SCZ. Paranoid SCZ and abnormal involuntary movements that indicate the orofacial type of TD are associated with the same genomic loci on chromosomes 3p22.2, 8q21.13, and 13q14.2. The limbtruncal type of TD is associated with a locus on chromosome 3p13 where the best functional candidate is FOXP1, a high-confidence SCZ gene. The results of this study shed light on common pathogenic mechanisms for SCZ and TD, and indicate that the pathogenesis of the orofacial and limbtruncal types of TD might be driven by interacting genes implicated in neurodevelopment.
AB - In the present study we conducted a genome-wide association study (GWAS) in a cohort of 505 patients with paranoid schizophrenia (SCZ), of which 95 had tardive dyskinesia (TD), and 503 healthy controls. Using data generated by the PsychENCODE Consortium (PEC) and other bioinformatic databases, we revealed a gene network, implicated in neurodevelopment and brain function, associated with both these disorders. Almost all these genes are in gene or isoform co-expression PEC network modules important for the functioning of the brain; the activity of these networks is also altered in SCZ, bipolar disorder and autism spectrum disorders. The associated PEC network modules are enriched for gene ontology terms relevant to the brain development and function (CNS development, neuron development, axon ensheathment, synapse, synaptic vesicle cycle, and signaling receptor activity) and to the immune system (inflammatory response). Results of the present study suggest that orofacial and limbtruncal types of TD seem to share the molecular network with SCZ. Paranoid SCZ and abnormal involuntary movements that indicate the orofacial type of TD are associated with the same genomic loci on chromosomes 3p22.2, 8q21.13, and 13q14.2. The limbtruncal type of TD is associated with a locus on chromosome 3p13 where the best functional candidate is FOXP1, a high-confidence SCZ gene. The results of this study shed light on common pathogenic mechanisms for SCZ and TD, and indicate that the pathogenesis of the orofacial and limbtruncal types of TD might be driven by interacting genes implicated in neurodevelopment.
KW - schizophrenia
KW - tardive dyskinesia
KW - GWAS
KW - Gene networks
KW - Regulatory sequence
KW - Schizophrenia
KW - Tardive dyskinesia
KW - Genome-Wide Association Study
KW - Humans
KW - Schizophrenia, Paranoid/drug therapy
KW - Tardive Dyskinesia/genetics
KW - Forkhead Transcription Factors/genetics
KW - Gene Regulatory Networks
KW - Repressor Proteins/genetics
KW - Antipsychotic Agents/adverse effects
KW - Alleles
KW - Polymorphism, Single Nucleotide
KW - APP
KW - RELIABILITY
KW - CAUSE INTELLECTUAL DISABILITY
KW - MOVEMENT-DISORDERS SADIMOD
KW - RISK-FACTORS
KW - TRANSCRIPTION
KW - AMYLOID PRECURSOR PROTEIN
KW - FOXP1
KW - FUNCTION MUTATIONS CAUSE
KW - INSIGHTS
UR - https://www.sciencedirect.com/science/article/abs/pii/S0278584620304504?via%3Dihub#!
UR - http://www.scopus.com/inward/record.url?scp=85093673577&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/93b7c46b-cd23-3a3c-bcd1-10a2b9a60ce4/
U2 - 10.1016/j.pnpbp.2020.110134
DO - 10.1016/j.pnpbp.2020.110134
M3 - Article
C2 - 33065217
AN - SCOPUS:85093673577
VL - 105
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
M1 - 110134
ER -
ID: 69855581