Genome-Wide Association Analysis with Gray Matter Volume as a Quantitative Phenotype in First-Episode Treatment-Naïve Patients with Schizophrenia

Abstract

Reduced Gray matter (GM) volume is a core feature of schizophrenia. Mapping genes that is associated with the heritable disease-related phenotypes may be conducive to elucidate the pathogenesis of schizophrenia. This study aims to identify the common genetic variants that underlie the deficits of GM volume in schizophrenia. High-resolution T1 images and whole genome genotyping data were obtained from 74 first-episode treatment-naïve patients with schizophrenia and 51 healthy controls in the Mental Health Centre of the West China Hospital, Sichuan University. All participants were scanned using a 3T MR imaging system and were genotyped using the HumanHap660 Bead Array. Reduced GM volumes in three brain areas including left hOC3v in the collateral sulcus of visual cortex (hOC3vL), left cerebellar vermis lobule 10 (vermisL10) and right cerebellar vermis lobule 10 (vermisR10) were found in patients with schizophrenia. There was a group by genotype interaction when genotypes from genome-wide scan were subsequently considered in the case-control analyses. SNPs from three genes or chromosomal regions (TBXAS1, PIK3C2G and HS3ST5) were identified to predict the changes of GM volume in hOC3vL, vermisL10 and vermisR10. These results also highlighted the usefulness of endophenotype in exploring the pathogenesis of neuropsychiatric diseases such as schizophrenia although further independent replication studies are needed in the future.

Morphological changes in gray matter volume correlate with catechol-O-methyl transferase gene Val158Met polymorphism in first-episode treatment-naïve patients with schizophrenia

“…Other than these regions, the cerebellum was traditionally supposed to be involved only in motor functions, but some studies have suggested its role in cognition and emotion [38] as well as in schizophrenia [39] . For example, abnormalities in the cerebellum and the occipital visual cortex have been detected in first-episode and/or drug-naïve patients [37,[40][41][42][43] using either the ROI approach or the voxel-based morphometry (VBM) method. In this study, the main effect of diagnosis on GMV suggested that the GM defi cits in schizophrenia might involve widespread regions and circuits in the brain.…”

Bipolar disorder risk gene FOXO6 modulates negative symptoms in schizophrenia: a neuroimaging genetics study

“…26 Evidence suggests that the risk for schizophrenia involves many genetic variants, each with small effects, 27 and the size of cohorts required to identify individual SNPs with such small effects is prohibitive. 28 Recent evidence, however, suggests that better homogeneity among cohorts could be more important than increasing sample sizes.…”

Neonatal amygdalae and hippocampi are influenced by genotype and prenatal environment, and reflected in the neonatal DNA methylome

“…1 Some measures of brain development, such as total brain volume, show strong heritability, while others, such as subcortical gray matter volume, show weaker heritability. [12][13][14] Recent large studies that have identified single nucleotide polymorphisms (SNPs) implicated in N-methyl-d-aspartate (NMDA) and dopamine signaling have shown robust associations with volumes of adult putamen and hippocampal brain regions, respectively. [12][13][14] Recent large studies that have identified single nucleotide polymorphisms (SNPs) implicated in N-methyl-d-aspartate (NMDA) and dopamine signaling have shown robust associations with volumes of adult putamen and hippocampal brain regions, respectively.…”