Genetic associations of brain structural networks in schizophrenia: a preliminary study.
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.


METHODS
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.
Jagannathan
Kanchana
K
Olin Neuropsychiatry Research Center, Institute of Living/Hartford Hospital, Hartford, Connecticut 06106, USA. Kjagannathan@harthosp.org
Calhoun
Vince D
VD
Gelernter
Joel
J
Stevens
Michael C
MC
Liu
Jingyu
J
Bolognani
Federico
F
Windemuth
Andreas
A
Ruaño
Gualberto
G
Assaf
Michal
M
Pearlson
Godfrey D
GD
D000328:Adult; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*
D009419:Nerve Tissue Proteins