A pilot multivariate parallel ICA study to investigate differential linkage between neural networks and genetic profiles in schizophrenia

Shashwath A. Meda, Kanchana Jagannathan, Joel Gelernter, Vince Daniel Calhoun, Jingyu Liu, Michael C. Stevens, Godfrey D. Pearlson

Research output: Contribution to journalArticle

Abstract

Understanding genetic influences on both healthy and disordered brain function is a major focus in psychiatric neuroimaging. We utilized task-related imaging findings from an fMRI auditory oddball task known to be robustly associated with abnormal activation in schizophrenia, to investigate genomic factors derived from multiple single nucleotide polymorphisms (SNPs) from genes previously shown to be associated with schizophrenia. Our major aim was to investigate the relationship of these genomic factors to normal/abnormal brain functionality between controls and schizophrenia patients. We studied a Caucasian-only sample of 35 healthy controls and 31 schizophrenia patients. All subjects performed an auditory oddball task, which consists of detecting an infrequent sound within a series of frequent sounds. Each subject was characterized on 24 different SNP markers spanning multiple risk genes previously associated with schizophrenia. We used a recently developed technique named parallel independent component analysis (para-ICA) to analyze this multimodal data set (Liu et al., 2008). The method aims to identify simultaneously independent components of each modality (functional imaging, genetics) and the relationships between them. We detected three fMRI components significantly correlated with two distinct gene components. The fMRI components, along with their significant genetic profile (dominant SNP) correlations were as follows: (1) Inferior frontal-anterior/posterior cingulate-thalamus-caudate with SNPs from Brain derived neurotropic factor (BDNF) and dopamine transporter (DAT) [. r= -0.51; p<0.0001], (2) superior/middle temporal gyrus-cingulate-premotor with SLC6A4_PR and SLC6A4_PR_AG (serotonin transporter promoter; 5HTTLPR) [. r= 0.27; p= 0.03], and (3) default mode-fronto-temporal gyrus with Brain derived neurotropic factor and dopamine transporter (BDNF, DAT) [. r= -0.25; p= 0.04]. Functional components comprised task-relevant regions (including PFC, ACC, STG and MTG) frequently identified as abnormal in schizophrenia. Further, gene-fMRI combinations 1 (Z= 1.75; p= 0.03), 2 (Z= 1.84; p= 0.03) and 3 (Z= 1.67; p= 0.04) listed above showed significant differences between controls and patients, based on their correlated loading coefficients. We demonstrate a framework to identify interactions between "clusters" of brain function and of genetic information. Our results reveal the effect/influence of specific interactions, (perhaps epistastatic in nature), between schizophrenia risk genes on imaging endophenotypes representing attention/working memory and goal directed related brain function, thus establishing a useful methodology to probe multivariate genotype-phenotype relationships.

Original languageEnglish (US)
Pages (from-to)1007-1015
Number of pages9
JournalNeuroImage
Volume53
Issue number3
DOIs
StatePublished - Nov 2010
Externally publishedYes

Fingerprint

Schizophrenia
Single Nucleotide Polymorphism
Brain
Magnetic Resonance Imaging
Dopamine Plasma Membrane Transport Proteins
Gyrus Cinguli
Temporal Lobe
Genes
Endophenotypes
Gene Components
Serotonin Plasma Membrane Transport Proteins
Thalamus
Short-Term Memory
Neuroimaging
Psychiatry
Genotype
Phenotype

Keywords

  • 5HTTLPR
  • Auditory oddball
  • BDNF
  • DAT
  • FMRI
  • Gene
  • Multivariate
  • Parallel ICA

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

Cite this

A pilot multivariate parallel ICA study to investigate differential linkage between neural networks and genetic profiles in schizophrenia. / Meda, Shashwath A.; Jagannathan, Kanchana; Gelernter, Joel; Calhoun, Vince Daniel; Liu, Jingyu; Stevens, Michael C.; Pearlson, Godfrey D.

In: NeuroImage, Vol. 53, No. 3, 11.2010, p. 1007-1015.

Research output: Contribution to journalArticle

Meda, Shashwath A. ; Jagannathan, Kanchana ; Gelernter, Joel ; Calhoun, Vince Daniel ; Liu, Jingyu ; Stevens, Michael C. ; Pearlson, Godfrey D. / A pilot multivariate parallel ICA study to investigate differential linkage between neural networks and genetic profiles in schizophrenia. In: NeuroImage. 2010 ; Vol. 53, No. 3. pp. 1007-1015.
@article{adaa5e7032b94006a2e969d1d38f24aa,
title = "A pilot multivariate parallel ICA study to investigate differential linkage between neural networks and genetic profiles in schizophrenia",
abstract = "Understanding genetic influences on both healthy and disordered brain function is a major focus in psychiatric neuroimaging. We utilized task-related imaging findings from an fMRI auditory oddball task known to be robustly associated with abnormal activation in schizophrenia, to investigate genomic factors derived from multiple single nucleotide polymorphisms (SNPs) from genes previously shown to be associated with schizophrenia. Our major aim was to investigate the relationship of these genomic factors to normal/abnormal brain functionality between controls and schizophrenia patients. We studied a Caucasian-only sample of 35 healthy controls and 31 schizophrenia patients. All subjects performed an auditory oddball task, which consists of detecting an infrequent sound within a series of frequent sounds. Each subject was characterized on 24 different SNP markers spanning multiple risk genes previously associated with schizophrenia. We used a recently developed technique named parallel independent component analysis (para-ICA) to analyze this multimodal data set (Liu et al., 2008). The method aims to identify simultaneously independent components of each modality (functional imaging, genetics) and the relationships between them. We detected three fMRI components significantly correlated with two distinct gene components. The fMRI components, along with their significant genetic profile (dominant SNP) correlations were as follows: (1) Inferior frontal-anterior/posterior cingulate-thalamus-caudate with SNPs from Brain derived neurotropic factor (BDNF) and dopamine transporter (DAT) [. r= -0.51; p<0.0001], (2) superior/middle temporal gyrus-cingulate-premotor with SLC6A4_PR and SLC6A4_PR_AG (serotonin transporter promoter; 5HTTLPR) [. r= 0.27; p= 0.03], and (3) default mode-fronto-temporal gyrus with Brain derived neurotropic factor and dopamine transporter (BDNF, DAT) [. r= -0.25; p= 0.04]. Functional components comprised task-relevant regions (including PFC, ACC, STG and MTG) frequently identified as abnormal in schizophrenia. Further, gene-fMRI combinations 1 (Z= 1.75; p= 0.03), 2 (Z= 1.84; p= 0.03) and 3 (Z= 1.67; p= 0.04) listed above showed significant differences between controls and patients, based on their correlated loading coefficients. We demonstrate a framework to identify interactions between {"}clusters{"} of brain function and of genetic information. Our results reveal the effect/influence of specific interactions, (perhaps epistastatic in nature), between schizophrenia risk genes on imaging endophenotypes representing attention/working memory and goal directed related brain function, thus establishing a useful methodology to probe multivariate genotype-phenotype relationships.",
keywords = "5HTTLPR, Auditory oddball, BDNF, DAT, FMRI, Gene, Multivariate, Parallel ICA",
author = "Meda, {Shashwath A.} and Kanchana Jagannathan and Joel Gelernter and Calhoun, {Vince Daniel} and Jingyu Liu and Stevens, {Michael C.} and Pearlson, {Godfrey D.}",
year = "2010",
month = "11",
doi = "10.1016/j.neuroimage.2009.11.052",
language = "English (US)",
volume = "53",
pages = "1007--1015",
journal = "NeuroImage",
issn = "1053-8119",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - A pilot multivariate parallel ICA study to investigate differential linkage between neural networks and genetic profiles in schizophrenia

AU - Meda, Shashwath A.

AU - Jagannathan, Kanchana

AU - Gelernter, Joel

AU - Calhoun, Vince Daniel

AU - Liu, Jingyu

AU - Stevens, Michael C.

AU - Pearlson, Godfrey D.

PY - 2010/11

Y1 - 2010/11

N2 - Understanding genetic influences on both healthy and disordered brain function is a major focus in psychiatric neuroimaging. We utilized task-related imaging findings from an fMRI auditory oddball task known to be robustly associated with abnormal activation in schizophrenia, to investigate genomic factors derived from multiple single nucleotide polymorphisms (SNPs) from genes previously shown to be associated with schizophrenia. Our major aim was to investigate the relationship of these genomic factors to normal/abnormal brain functionality between controls and schizophrenia patients. We studied a Caucasian-only sample of 35 healthy controls and 31 schizophrenia patients. All subjects performed an auditory oddball task, which consists of detecting an infrequent sound within a series of frequent sounds. Each subject was characterized on 24 different SNP markers spanning multiple risk genes previously associated with schizophrenia. We used a recently developed technique named parallel independent component analysis (para-ICA) to analyze this multimodal data set (Liu et al., 2008). The method aims to identify simultaneously independent components of each modality (functional imaging, genetics) and the relationships between them. We detected three fMRI components significantly correlated with two distinct gene components. The fMRI components, along with their significant genetic profile (dominant SNP) correlations were as follows: (1) Inferior frontal-anterior/posterior cingulate-thalamus-caudate with SNPs from Brain derived neurotropic factor (BDNF) and dopamine transporter (DAT) [. r= -0.51; p<0.0001], (2) superior/middle temporal gyrus-cingulate-premotor with SLC6A4_PR and SLC6A4_PR_AG (serotonin transporter promoter; 5HTTLPR) [. r= 0.27; p= 0.03], and (3) default mode-fronto-temporal gyrus with Brain derived neurotropic factor and dopamine transporter (BDNF, DAT) [. r= -0.25; p= 0.04]. Functional components comprised task-relevant regions (including PFC, ACC, STG and MTG) frequently identified as abnormal in schizophrenia. Further, gene-fMRI combinations 1 (Z= 1.75; p= 0.03), 2 (Z= 1.84; p= 0.03) and 3 (Z= 1.67; p= 0.04) listed above showed significant differences between controls and patients, based on their correlated loading coefficients. We demonstrate a framework to identify interactions between "clusters" of brain function and of genetic information. Our results reveal the effect/influence of specific interactions, (perhaps epistastatic in nature), between schizophrenia risk genes on imaging endophenotypes representing attention/working memory and goal directed related brain function, thus establishing a useful methodology to probe multivariate genotype-phenotype relationships.

AB - Understanding genetic influences on both healthy and disordered brain function is a major focus in psychiatric neuroimaging. We utilized task-related imaging findings from an fMRI auditory oddball task known to be robustly associated with abnormal activation in schizophrenia, to investigate genomic factors derived from multiple single nucleotide polymorphisms (SNPs) from genes previously shown to be associated with schizophrenia. Our major aim was to investigate the relationship of these genomic factors to normal/abnormal brain functionality between controls and schizophrenia patients. We studied a Caucasian-only sample of 35 healthy controls and 31 schizophrenia patients. All subjects performed an auditory oddball task, which consists of detecting an infrequent sound within a series of frequent sounds. Each subject was characterized on 24 different SNP markers spanning multiple risk genes previously associated with schizophrenia. We used a recently developed technique named parallel independent component analysis (para-ICA) to analyze this multimodal data set (Liu et al., 2008). The method aims to identify simultaneously independent components of each modality (functional imaging, genetics) and the relationships between them. We detected three fMRI components significantly correlated with two distinct gene components. The fMRI components, along with their significant genetic profile (dominant SNP) correlations were as follows: (1) Inferior frontal-anterior/posterior cingulate-thalamus-caudate with SNPs from Brain derived neurotropic factor (BDNF) and dopamine transporter (DAT) [. r= -0.51; p<0.0001], (2) superior/middle temporal gyrus-cingulate-premotor with SLC6A4_PR and SLC6A4_PR_AG (serotonin transporter promoter; 5HTTLPR) [. r= 0.27; p= 0.03], and (3) default mode-fronto-temporal gyrus with Brain derived neurotropic factor and dopamine transporter (BDNF, DAT) [. r= -0.25; p= 0.04]. Functional components comprised task-relevant regions (including PFC, ACC, STG and MTG) frequently identified as abnormal in schizophrenia. Further, gene-fMRI combinations 1 (Z= 1.75; p= 0.03), 2 (Z= 1.84; p= 0.03) and 3 (Z= 1.67; p= 0.04) listed above showed significant differences between controls and patients, based on their correlated loading coefficients. We demonstrate a framework to identify interactions between "clusters" of brain function and of genetic information. Our results reveal the effect/influence of specific interactions, (perhaps epistastatic in nature), between schizophrenia risk genes on imaging endophenotypes representing attention/working memory and goal directed related brain function, thus establishing a useful methodology to probe multivariate genotype-phenotype relationships.

KW - 5HTTLPR

KW - Auditory oddball

KW - BDNF

KW - DAT

KW - FMRI

KW - Gene

KW - Multivariate

KW - Parallel ICA

UR - http://www.scopus.com/inward/record.url?scp=77956228096&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956228096&partnerID=8YFLogxK

U2 - 10.1016/j.neuroimage.2009.11.052

DO - 10.1016/j.neuroimage.2009.11.052

M3 - Article

C2 - 19944766

AN - SCOPUS:77956228096

VL - 53

SP - 1007

EP - 1015

JO - NeuroImage

JF - NeuroImage

SN - 1053-8119

IS - 3

ER -