Genetic influences of resting state fMRI activity in language-related brain regions in healthy controls and schizophrenia patients: a pilot study

Abstract

Individuals with schizophrenia show a broad range of language impairments, similar to those observed in reading disability (RD). Genetic linkage and association studies of RD have identified a number of candidate RD-genes that are associated with neuronal migration. Some individuals with schizophrenia also show evidence of impaired cortical neuronal migration. We have previously linked RD-related genes with gray matter distributions in healthy controls and schizophrenia. The aim of the current study was to extend these structural findings and to examine links between putative RD-genes and functional connectivity of language-related regions in healthy controls (n = 27) and schizophrenia (n = 28). Parallel independent component analysis (parallel-ICA) was used to examine the relationship between language-related regions extracted from resting-state fMRI and 16 single nucleotide polymorphisms (SNPs) spanning 5 RD-related genes. Parallel-ICA identified four significant fMRI-SNP relationships. A Left Broca-Superior/Inferior Parietal network was related to two KIAA0319 SNPs in controls but not in schizophrenia. For both diagnostic groups, a Broca-Medial Parietal network was related to two DCDC2 SNPs, while a Left Wernicke-Fronto-Occipital network was related to two KIAA0319 SNPs. A Bilateral Wernicke-Fronto-Parietal network was related to one KIAA0319 SNP only in controls. Thus, RD-genes influence functional connectivity in language-related regions, but no RD-gene uniquely affected network function in schizophrenia as compared to controls. This is in contrast with our previous study where RD-genes affected gray matter distribution in some structural networks in schizophrenia but not in controls. Thus these RD-genes may exert a more important influence on structure rather than function of language-related networks in schizophrenia.

Fig 1

fMRI and SNP components for (A) Left Broca-Parietal and (B) Broca-Medial Parietal networks. Scatterplots show relationship between loading coefficients from fMRI and SNP components

Fig 2

fMRI for (A) Left Wernicke-Fronto-Occipital and (B) Bilateral Wernicke-Fronto-Parietal networks. Scatterplots show relationship between loading coefficients for fMRI and SNP components. For visualization purposes, the outlier present in Left Wernicke-Fronto-Occipital network has been removed

Fig 3

Linkage disequilibrium between chromosome 6 markers. LD values are r², the correlation coefficient between markers.