TY - JOUR
T1 - Genetic associations of brain structural networks in schizophrenia
T2 - A preliminary study
AU - Jagannathan, Kanchana
AU - Calhoun, Vince D.
AU - Gelernter, Joel
AU - Stevens, Michael C.
AU - Liu, Jingyu
AU - Bolognani, Federico
AU - Windemuth, Andreas
AU - Ruao, Gualberto
AU - Assaf, Michal
AU - Pearlson, Godfrey D.
N1 - Funding Information:
This research was supported by the National Institutes of Health under Grant Nos. R37 MH43775 , R01 MH074797 , and R01 MH077945 (to GP); R01 EB005846 and R01 EB006841 (to VDC); and R43 MH075481 (to GR). We thank the research staff at the Olin Neuropsychiatry Research Center who helped to collect the data.
PY - 2010/10/1
Y1 - 2010/10/1
N2 - Background: Schizophrenia is a complex genetic disorder, with multiple putative risk genes and many reports of reduced cortical gray matter. Identifying the genetic loci contributing to these structural alterations in schizophrenia (and likely also to normal structural gray matter patterns) could aid understanding of schizophrenia's pathophysiology. We used structural parameters as potential intermediate illness markers to investigate genomic factors derived from single nucleotide polymorphism (SNP) arrays. Method: We used research quality structural magnetic resonance imaging (sMRI) scans from European American subjects including 33 healthy control subjects and 18 schizophrenia patients. All subjects were genotyped for 367 SNPs. Linked sMRI and genetic (SNP) components were extracted to reveal relationships between brain structure and SNPs, using parallel independent component analysis, a novel multivariate approach that operates effectively in small sample sizes. Results: We identified an sMRI component that significantly correlated with a genetic component (r = -.536, p < .00005); components also distinguished groups. In the sMRI component, schizophrenia gray matter deficits were in brain regions consistently implicated in previous reports, including frontal and temporal lobes and thalamus (p < .01). These deficits were related to SNPs from 16 genes, several previously associated with schizophrenia risk and/or involved in normal central nervous system development, including AKT, PI3K, SLC6A4, DRD2, CHRM2, and ADORA2A. Conclusions: Despite the small sample size, this novel analysis method identified an sMRI component including brain areas previously reported to be abnormal in schizophrenia and an associated genetic component containing several putative schizophrenia risk genes. Thus, we identified multiple genes potentially underlying specific structural brain abnormalities in schizophrenia.
AB - Background: Schizophrenia is a complex genetic disorder, with multiple putative risk genes and many reports of reduced cortical gray matter. Identifying the genetic loci contributing to these structural alterations in schizophrenia (and likely also to normal structural gray matter patterns) could aid understanding of schizophrenia's pathophysiology. We used structural parameters as potential intermediate illness markers to investigate genomic factors derived from single nucleotide polymorphism (SNP) arrays. Method: We used research quality structural magnetic resonance imaging (sMRI) scans from European American subjects including 33 healthy control subjects and 18 schizophrenia patients. All subjects were genotyped for 367 SNPs. Linked sMRI and genetic (SNP) components were extracted to reveal relationships between brain structure and SNPs, using parallel independent component analysis, a novel multivariate approach that operates effectively in small sample sizes. Results: We identified an sMRI component that significantly correlated with a genetic component (r = -.536, p < .00005); components also distinguished groups. In the sMRI component, schizophrenia gray matter deficits were in brain regions consistently implicated in previous reports, including frontal and temporal lobes and thalamus (p < .01). These deficits were related to SNPs from 16 genes, several previously associated with schizophrenia risk and/or involved in normal central nervous system development, including AKT, PI3K, SLC6A4, DRD2, CHRM2, and ADORA2A. Conclusions: Despite the small sample size, this novel analysis method identified an sMRI component including brain areas previously reported to be abnormal in schizophrenia and an associated genetic component containing several putative schizophrenia risk genes. Thus, we identified multiple genes potentially underlying specific structural brain abnormalities in schizophrenia.
KW - Brain development
KW - genetics
KW - imaging
KW - schizophrenia
KW - structural magnetic resonance imaging (sMRI)
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U2 - 10.1016/j.biopsych.2010.06.002
DO - 10.1016/j.biopsych.2010.06.002
M3 - Article
C2 - 20691427
AN - SCOPUS:77956903708
SN - 0006-3223
VL - 68
SP - 657
EP - 666
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 7
ER -