TY - JOUR
T1 - Multivariate genetic correlates of the auditory paired stimuli-based p2 event-related potential in the psychosis dimension from the BSNIP study
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.
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
PY - 2016/5/1
Y1 - 2016/5/1
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.
KW - bipolar disorder
KW - event-related potential
KW - gene
KW - pathway
KW - psychosis
KW - schizophrenia
KW - single nucleotide polymorphism
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U2 - 10.1093/schbul/sbv147
DO - 10.1093/schbul/sbv147
M3 - Article
C2 - 26462502
AN - SCOPUS:84966349348
SN - 0586-7614
VL - 42
SP - 851
EP - 862
JO - Schizophrenia bulletin
JF - Schizophrenia bulletin
IS - 3
ER -