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Evidence for genetic contribution to the increased risk of type 2 diabetes in schizophrenia.
Transl. Psychiatry 8:252 (2018)
The epidemiologic link between schizophrenia (SCZ) and type 2 diabetes (T2D) remains poorly understood. Here, we investigate the presence and extent of a shared genetic background between SCZ and T2D using genome-wide approaches. We performed a genome-wide association study (GWAS) and polygenic risk score analysis in a Greek sample collection (GOMAP) comprising three patient groups: SCZ only (n = 924), T2D only (n = 822), comorbid SCZ and T2D (n = 505); samples from two separate Greek cohorts were used as population-based controls (n = 1,125). We used genome-wide summary statistics from two large-scale GWAS of SCZ and T2D from the PGC and DIAGRAM consortia, respectively, to perform genetic overlap analyses, including a regional colocalisation test. We show for the first time that patients with comorbid SCZ and T2D have a higher genetic predisposition to both disorders compared to controls. We identify five genomic regions with evidence of colocalising SCZ and T2D signals, three of which contain known loci for both diseases. We also observe a significant excess of shared association signals between SCZ and T2D at nine out of ten investigated p value thresholds. Finally, we identify 29 genes associated with both T2D and SCZ, several of which have been implicated in biological processes relevant to these disorders. Together our results demonstrate that the observed comorbidity between SCZ and T2D is at least in part due to shared genetic mechanisms.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genome-wide Association; Susceptibility Loci; Polygenic Risk; Architecture; Mellitus; Insights; People; Antipsychotics; Variants; Diseases
ISSN (print) / ISBN
2158-3188
e-ISSN
2158-3188
Journal
Translational Psychiatry
Quellenangaben
Volume: 8,
Issue: 1,
Article Number: 252
Publisher
Nature Publishing Group
Publishing Place
75 Varick St, 9th Flr, New York, Ny 10013-1917 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Translational Genomics (ITG)