A szkizofrénia multilókusz genetikai vizsgálata az idegfejlödés és az immunrendszer zavarának oki szerepére utal(hat)

Translated title of the contribution: Multilocus genetic analysis implicates neurodevelopment and immune system in the etiology of schizophrenia

Attila József Pulay, Júlia Koller, L. Nagy, Maria Judit Molnár, J. Réthelyi

Research output: Contribution to journalArticle

Abstract

Background - Schizophrenia is a severe psychiatric disorder of poorly understood etiology, characterized by high heritability, multifactorial inheritance and high heterogeneity. Multilocus associaton methods may reduce the genetic heterogeneity and improve the probability of replication between analyses. Objectives -The aims of our study were twofold: 1. To analyse genetic risk factors of schizophrenia by using multi- locus genetic tests. 2. To assess the replication probability attributable to the various multilocus tests. Subjects - Discovery set: case-parent trios of unaffected parents and affected probands with a DSM-IV schizophrenia diagnosis (n=16); replication set: schizophrenia cases and unaffected controls (n=5337). Methods -Associations of single nucleotide and indel markers were transferred to gene-And geneset-based associations, furthermore to geneset-enrichment tests and functional annotation cluster analyses in a two-staged designs. Associations with p<0.1 from the discovery set were tested in the replication sample. Familywise p-value correction for multiple comparisons were performed during the replication step. Results -After correction for multiplicity, no significant association or enrichment were detected for gene-based nor canonical pathway analyses, but significant association of the 14q31 cytoband and enrichments of the 5q31 and Xql3 cytobands were found (pcorr: 0.002, 0.006 and 0.048, respectively). Functional annotation clustering yielded statistically significant enrichment scores for clusters of splicing/alternative splicing, neurodevelopment and embryonic development. Improvements in replication probabilty were found with increased test complexity (Prep: 0, 0.015, 0.21). Conclusions - Our results corroborate the involvement of neurodevelopment, synaptic plasticity and immune mechanisms in the etiology of schizophrenia. Also, our findings indicated improvement of replication probability by using multilocus genetic analyses.

Original languageHungarian
Pages (from-to)115-126
Number of pages12
JournalIdeggyogyaszati Szemle
Volume70
Issue number3-4
DOIs
Publication statusPublished - Mar 30 2017

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Immune System
Schizophrenia
Cluster Analysis
Multifactorial Inheritance
Neuronal Plasticity
Genetic Loci
Genetic Heterogeneity
Alternative Splicing
Diagnostic and Statistical Manual of Mental Disorders
Genes
Embryonic Development
Psychiatry
Nucleotides

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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A szkizofrénia multilókusz genetikai vizsgálata az idegfejlödés és az immunrendszer zavarának oki szerepére utal(hat). / Pulay, Attila József; Koller, Júlia; Nagy, L.; Molnár, Maria Judit; Réthelyi, J.

In: Ideggyogyaszati Szemle, Vol. 70, No. 3-4, 30.03.2017, p. 115-126.

Research output: Contribution to journalArticle

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abstract = "Background - Schizophrenia is a severe psychiatric disorder of poorly understood etiology, characterized by high heritability, multifactorial inheritance and high heterogeneity. Multilocus associaton methods may reduce the genetic heterogeneity and improve the probability of replication between analyses. Objectives -The aims of our study were twofold: 1. To analyse genetic risk factors of schizophrenia by using multi- locus genetic tests. 2. To assess the replication probability attributable to the various multilocus tests. Subjects - Discovery set: case-parent trios of unaffected parents and affected probands with a DSM-IV schizophrenia diagnosis (n=16); replication set: schizophrenia cases and unaffected controls (n=5337). Methods -Associations of single nucleotide and indel markers were transferred to gene-And geneset-based associations, furthermore to geneset-enrichment tests and functional annotation cluster analyses in a two-staged designs. Associations with p<0.1 from the discovery set were tested in the replication sample. Familywise p-value correction for multiple comparisons were performed during the replication step. Results -After correction for multiplicity, no significant association or enrichment were detected for gene-based nor canonical pathway analyses, but significant association of the 14q31 cytoband and enrichments of the 5q31 and Xql3 cytobands were found (pcorr: 0.002, 0.006 and 0.048, respectively). Functional annotation clustering yielded statistically significant enrichment scores for clusters of splicing/alternative splicing, neurodevelopment and embryonic development. Improvements in replication probabilty were found with increased test complexity (Prep: 0, 0.015, 0.21). Conclusions - Our results corroborate the involvement of neurodevelopment, synaptic plasticity and immune mechanisms in the etiology of schizophrenia. Also, our findings indicated improvement of replication probability by using multilocus genetic analyses.",
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AU - Koller, Júlia

AU - Nagy, L.

AU - Molnár, Maria Judit

AU - Réthelyi, J.

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AB - Background - Schizophrenia is a severe psychiatric disorder of poorly understood etiology, characterized by high heritability, multifactorial inheritance and high heterogeneity. Multilocus associaton methods may reduce the genetic heterogeneity and improve the probability of replication between analyses. Objectives -The aims of our study were twofold: 1. To analyse genetic risk factors of schizophrenia by using multi- locus genetic tests. 2. To assess the replication probability attributable to the various multilocus tests. Subjects - Discovery set: case-parent trios of unaffected parents and affected probands with a DSM-IV schizophrenia diagnosis (n=16); replication set: schizophrenia cases and unaffected controls (n=5337). Methods -Associations of single nucleotide and indel markers were transferred to gene-And geneset-based associations, furthermore to geneset-enrichment tests and functional annotation cluster analyses in a two-staged designs. Associations with p<0.1 from the discovery set were tested in the replication sample. Familywise p-value correction for multiple comparisons were performed during the replication step. Results -After correction for multiplicity, no significant association or enrichment were detected for gene-based nor canonical pathway analyses, but significant association of the 14q31 cytoband and enrichments of the 5q31 and Xql3 cytobands were found (pcorr: 0.002, 0.006 and 0.048, respectively). Functional annotation clustering yielded statistically significant enrichment scores for clusters of splicing/alternative splicing, neurodevelopment and embryonic development. Improvements in replication probabilty were found with increased test complexity (Prep: 0, 0.015, 0.21). Conclusions - Our results corroborate the involvement of neurodevelopment, synaptic plasticity and immune mechanisms in the etiology of schizophrenia. Also, our findings indicated improvement of replication probability by using multilocus genetic analyses.

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