Multivariate genetic correlates of the auditory paired stimuli-based p2 event-related potential in the psychosis dimension from the BSNIP study

Mohammadreza Mokhtari, Balaji Narayanan, Jordan P. Hamm, Pauline Soh, Vince D. Calhoun, Gualberto Ruaño, Mohan Kocherla, Andreas Windemuth, Brett A. Clementz, Carol A. Tamminga, John A. Sweeney, Matcheri S. Keshavan, Godfrey D. Pearlson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: The complex molecular etiology of psychosis in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is not well defined, presumably due to their multifactorial genetic architecture. Neurobiological correlates of psychosis can be identified through genetic associations of intermediate phenotypes such as event-related potential (ERP) from auditory paired stimulus processing (APSP). Various ERP components of APSP are heritable and aberrant in SZ, PBP and their relatives, but their multivariate genetic factors are less explored. Methods: We investigated the multivariate polygenic association of ERP from 64-sensor auditory paired stimulus data in 149 SZ, 209 PBP probands, and 99 healthy individuals from the multisite Bipolar-Schizophrenia Network on Intermediate Phenotypes study. Multivariate association of 64-channel APSP waveforms with a subset of 16 999 single nucleotide polymorphisms (SNPs) (reduced from 1 million SNP array) was examined using parallel independent component analysis (Para-ICA). Biological pathways associated with the genes were assessed using enrichment-based analysis tools. Results: Para-ICA identified 2 ERP components, of which one was significantly correlated with a genetic network comprising multiple linearly coupled gene variants that explained ~4% of the ERP phenotype variance. Enrichment analysis revealed epidermal growth factor, endocannabinoid signaling, glutamatergic synapse and maltohexaose transport associated with P2 component of the N1-P2 ERP waveform. This ERP component also showed deficits in SZ and PBP. Conclusions: Aberrant P2 component in psychosis was associated with gene networks regulating several fundamental biologic functions, either general or specific to nervous system development. The pathways and processes underlying the gene clusters play a crucial role in brain function, plausibly implicated in psychosis.

Original languageEnglish (US)
Pages (from-to)851-862
Number of pages12
JournalSchizophrenia Bulletin
Volume42
Issue number3
DOIs
StatePublished - May 1 2016

Fingerprint

Evoked Potentials
Psychotic Disorders
Schizophrenia
Bipolar Disorder
Phenotype
Single Nucleotide Polymorphism
Endocannabinoids
Gene Regulatory Networks
Multigene Family
Epidermal Growth Factor
Synapses
Nervous System
Genes
Brain

Keywords

  • bipolar disorder
  • event-related potential
  • gene
  • pathway
  • psychosis
  • schizophrenia
  • single nucleotide polymorphism

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Multivariate genetic correlates of the auditory paired stimuli-based p2 event-related potential in the psychosis dimension from the BSNIP study. / Mokhtari, Mohammadreza; Narayanan, Balaji; Hamm, Jordan P.; Soh, Pauline; Calhoun, Vince D.; Ruaño, Gualberto; Kocherla, Mohan; Windemuth, Andreas; Clementz, Brett A.; Tamminga, Carol A.; Sweeney, John A.; Keshavan, Matcheri S.; Pearlson, Godfrey D.

In: Schizophrenia Bulletin, Vol. 42, No. 3, 01.05.2016, p. 851-862.

Research output: Contribution to journalArticle

Mokhtari, M, Narayanan, B, Hamm, JP, Soh, P, Calhoun, VD, Ruaño, G, Kocherla, M, Windemuth, A, Clementz, BA, Tamminga, CA, Sweeney, JA, Keshavan, MS & Pearlson, GD 2016, 'Multivariate genetic correlates of the auditory paired stimuli-based p2 event-related potential in the psychosis dimension from the BSNIP study', Schizophrenia Bulletin, vol. 42, no. 3, pp. 851-862. https://doi.org/10.1093/schbul/sbv147
Mokhtari, Mohammadreza ; Narayanan, Balaji ; Hamm, Jordan P. ; Soh, Pauline ; Calhoun, Vince D. ; Ruaño, Gualberto ; Kocherla, Mohan ; Windemuth, Andreas ; Clementz, Brett A. ; Tamminga, Carol A. ; Sweeney, John A. ; Keshavan, Matcheri S. ; Pearlson, Godfrey D. / Multivariate genetic correlates of the auditory paired stimuli-based p2 event-related potential in the psychosis dimension from the BSNIP study. In: Schizophrenia Bulletin. 2016 ; Vol. 42, No. 3. pp. 851-862.
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abstract = "Objective: The complex molecular etiology of psychosis in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is not well defined, presumably due to their multifactorial genetic architecture. Neurobiological correlates of psychosis can be identified through genetic associations of intermediate phenotypes such as event-related potential (ERP) from auditory paired stimulus processing (APSP). Various ERP components of APSP are heritable and aberrant in SZ, PBP and their relatives, but their multivariate genetic factors are less explored. Methods: We investigated the multivariate polygenic association of ERP from 64-sensor auditory paired stimulus data in 149 SZ, 209 PBP probands, and 99 healthy individuals from the multisite Bipolar-Schizophrenia Network on Intermediate Phenotypes study. Multivariate association of 64-channel APSP waveforms with a subset of 16 999 single nucleotide polymorphisms (SNPs) (reduced from 1 million SNP array) was examined using parallel independent component analysis (Para-ICA). Biological pathways associated with the genes were assessed using enrichment-based analysis tools. Results: Para-ICA identified 2 ERP components, of which one was significantly correlated with a genetic network comprising multiple linearly coupled gene variants that explained ~4{\%} of the ERP phenotype variance. Enrichment analysis revealed epidermal growth factor, endocannabinoid signaling, glutamatergic synapse and maltohexaose transport associated with P2 component of the N1-P2 ERP waveform. This ERP component also showed deficits in SZ and PBP. Conclusions: Aberrant P2 component in psychosis was associated with gene networks regulating several fundamental biologic functions, either general or specific to nervous system development. The pathways and processes underlying the gene clusters play a crucial role in brain function, plausibly implicated in psychosis.",
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AU - Mokhtari, Mohammadreza

AU - Narayanan, Balaji

AU - Hamm, Jordan P.

AU - Soh, Pauline

AU - Calhoun, Vince D.

AU - Ruaño, Gualberto

AU - Kocherla, Mohan

AU - Windemuth, Andreas

AU - Clementz, Brett A.

AU - Tamminga, Carol A.

AU - Sweeney, John A.

AU - Keshavan, Matcheri S.

AU - Pearlson, Godfrey D.

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N2 - Objective: The complex molecular etiology of psychosis in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is not well defined, presumably due to their multifactorial genetic architecture. Neurobiological correlates of psychosis can be identified through genetic associations of intermediate phenotypes such as event-related potential (ERP) from auditory paired stimulus processing (APSP). Various ERP components of APSP are heritable and aberrant in SZ, PBP and their relatives, but their multivariate genetic factors are less explored. Methods: We investigated the multivariate polygenic association of ERP from 64-sensor auditory paired stimulus data in 149 SZ, 209 PBP probands, and 99 healthy individuals from the multisite Bipolar-Schizophrenia Network on Intermediate Phenotypes study. Multivariate association of 64-channel APSP waveforms with a subset of 16 999 single nucleotide polymorphisms (SNPs) (reduced from 1 million SNP array) was examined using parallel independent component analysis (Para-ICA). Biological pathways associated with the genes were assessed using enrichment-based analysis tools. Results: Para-ICA identified 2 ERP components, of which one was significantly correlated with a genetic network comprising multiple linearly coupled gene variants that explained ~4% of the ERP phenotype variance. Enrichment analysis revealed epidermal growth factor, endocannabinoid signaling, glutamatergic synapse and maltohexaose transport associated with P2 component of the N1-P2 ERP waveform. This ERP component also showed deficits in SZ and PBP. Conclusions: Aberrant P2 component in psychosis was associated with gene networks regulating several fundamental biologic functions, either general or specific to nervous system development. The pathways and processes underlying the gene clusters play a crucial role in brain function, plausibly implicated in psychosis.

AB - Objective: The complex molecular etiology of psychosis in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is not well defined, presumably due to their multifactorial genetic architecture. Neurobiological correlates of psychosis can be identified through genetic associations of intermediate phenotypes such as event-related potential (ERP) from auditory paired stimulus processing (APSP). Various ERP components of APSP are heritable and aberrant in SZ, PBP and their relatives, but their multivariate genetic factors are less explored. Methods: We investigated the multivariate polygenic association of ERP from 64-sensor auditory paired stimulus data in 149 SZ, 209 PBP probands, and 99 healthy individuals from the multisite Bipolar-Schizophrenia Network on Intermediate Phenotypes study. Multivariate association of 64-channel APSP waveforms with a subset of 16 999 single nucleotide polymorphisms (SNPs) (reduced from 1 million SNP array) was examined using parallel independent component analysis (Para-ICA). Biological pathways associated with the genes were assessed using enrichment-based analysis tools. Results: Para-ICA identified 2 ERP components, of which one was significantly correlated with a genetic network comprising multiple linearly coupled gene variants that explained ~4% of the ERP phenotype variance. Enrichment analysis revealed epidermal growth factor, endocannabinoid signaling, glutamatergic synapse and maltohexaose transport associated with P2 component of the N1-P2 ERP waveform. This ERP component also showed deficits in SZ and PBP. Conclusions: Aberrant P2 component in psychosis was associated with gene networks regulating several fundamental biologic functions, either general or specific to nervous system development. The pathways and processes underlying the gene clusters play a crucial role in brain function, plausibly implicated in psychosis.

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KW - single nucleotide polymorphism

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