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Abstract
Objectives. Schizophrenia is a highly disabling psychiatric disorder with a heterogeneous phenotypic appearance. We aimed to further the understanding of some of the underlying genetics of schizophrenia, using left superior temporal gyrus (STG) grey matter thickness reduction as an endophenoptype in a genome-wide association (GWA) study. Methods. Structural magnetic resonance imaging (MRI) and genetic data of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia were used to analyse the interaction effects between 1,067,955 single nucleotide polymorphisms (SNPs) and disease status on left STG thickness in 126 healthy controls and 113 patients with schizophrenia. We next used a pathway approach to detect underlying pathophysiological pathways that may be related to schizophrenia. Results. No SNP by diagnosis interaction effect reached genome-wide significance (5 × 10–8) in our GWA study, but 10 SNPs reached P-values less than 10–6. The most prominent pathways included those involved in insulin, calcium, PI3K-Akt and MAPK signalling. Conclusions. Our strongest findings in the GWA study and pathway analysis point towards an involvement of glucose metabolism in left STG thickness reduction in patients with schizophrenia only. These results are in line with recently published studies, which showed an increased prevalence of psychosis among patients with metabolic syndrome-related illnesses including diabetes.
Acknowledgements
This work was supported by the National Institutes of Health (NIH/NCRR P41RR14075), Department of Energy (DE-FG02-99ER62764), MIND Research Network, Morphometry Biomedical Informatics Research Network (BIRN) (1U24, RR021382A), Function BIRN (U24RR021992-01, NIH.NCRR MO1 RR025758-01, NIMH 1RC1MH089257 to VDC), the NARSAD Young Investigator Grant (to SE), and the Deutsche Forschungsgemeinschaft (Research Fellowship to SE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Statement of Interest
Veit Roessner has received lecture fees from Eli Lilly, Janssen-Cilag, Medice, and Novartis and was a member of advisory boards of Eli Lilly, Novartis. All other authors declare no biomedical financial interests or other potential conflict of interests.
Supplementary material available online
Supplementary Figure 1.1: Hallucination scores are negatively correlated with left superior temporal gyrus (lSTG) thickness measures.
Supplementary Table 2.1: Principal component statistics from the MCIC Eigenstrat analysis.
Supplementary Table 3.1: Clinical variables of patients with SZ.
Supplementary Table 3.2: Distribution of genotypes, call rate and Hardy-Weinberg equilibrium for main hits in the MCIC sample.
Supplementary Figure 3.1: Quantile-quantile plot.
Supplementary Figure 3.2: Linkage disequilibrium (LD) plot.
Supplementary Table 3.3: Pathway approach results of the gene-based analysis tool VEGAS.
Supplementary Table 3.4: KEGG Pathway Database Pathways and corresponding genes available online at http://informahealthcare.com/doi/abs/10.3109/15622975.2015.1062915.