title: Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study.
abstract: Schizophrenia (SZ) and psychotic bipolar disorder (PBP) are disabling psychiatric illnesses with complex and unclear etiologies. Electroencephalogram (EEG) oscillatory abnormalities in SZ and PBP probands are heritable and expressed in their relatives, but the neurobiology and genetic factors mediating these abnormalities in the psychosis dimension of either disorder are less explored. We examined the polygenic architecture of eyes-open resting state EEG frequency activity (intrinsic frequency) from 64 channels in 105 SZ, 145 PBP probands and 56 healthy controls (HCs) from the multisite BSNIP (Bipolar-Schizophrenia Network on Intermediate Phenotypes) study. One million single-nucleotide polymorphisms (SNPs) were derived from DNA. We assessed eight data-driven EEG frequency activity derived from group-independent component analysis (ICA) in conjunction with a reduced subset of 10,422 SNPs through novel multivariate association using parallel ICA (para-ICA). Genes contributing to the association were examined collectively using pathway analysis tools. Para-ICA extracted five frequency and nine SNP components, of which theta and delta activities were significantly correlated with two different gene components, comprising genes participating extensively in brain development, neurogenesis and synaptogenesis. Delta and theta abnormality was present in both SZ and PBP, while theta differed between the two disorders. Theta abnormalities were also mediated by gene clusters involved in glutamic acid pathways, cadherin and synaptic contact-based cell adhesion processes. Our data suggest plausible multifactorial genetic networks, including novel and several previously identified (DISC1) candidate risk genes, mediating low frequency delta and theta abnormalities in psychoses. The gene clusters were enriched for biological properties affecting neural circuitry and involved in brain function and/or development.
authors.affiliation: Olin Neuropsychiatry Research Center, Hartford Hospital, Institute of Living, Hartford, CT, USA.
authors.forename: B
authors.initials: B
authors.lastname: Narayanan
authors.affiliation: Olin Neuropsychiatry Research Center, Hartford Hospital, Institute of Living, Hartford, CT, USA.
authors.forename: P
authors.initials: P
authors.lastname: Soh
authors.affiliation: 1] Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA [2] The Mind Research Network, Albuquerque, NM, USA.
authors.forename: V D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: 1] Genetics Research Center, Hartford Hospital, Hartford, CT, USA [2] Genomas Inc, Hartford, CT, USA.
authors.forename: G
authors.initials: G
authors.lastname: Ruaño
authors.affiliation: 1] Genetics Research Center, Hartford Hospital, Hartford, CT, USA [2] Genomas Inc, Hartford, CT, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kocherla
authors.affiliation: Genetics Research Center, Hartford Hospital, Hartford, CT, USA.
authors.forename: A
authors.initials: A
authors.lastname: Windemuth
authors.affiliation: Department of Psychology, University of Georgia, Athens, GA, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Clementz
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Tamminga
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Sweeney
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Keshavan
authors.affiliation: 1] Olin Neuropsychiatry Research Center, Hartford Hospital, Institute of Living, Hartford, CT, USA [2] Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA [3] Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Pearlson
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000254:growth & development; D058256:Brain Waves / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000235:genetics; D003700:Delta Rhythm / Q000235:genetics* / Q000502:physiology; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D055495:Neurogenesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D013826:Theta Rhythm / Q000235:genetics* / Q000502:physiology; D055815:Young Adult