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Hackinger, S.* ; Prins, B.* ; Mamakou, V.* ; Zengini, E.* ; Marouli, E.* ; Brčić, L.* ; Serafetinidis, I.* ; Lamnissou, K.* ; Kontaxakis, V.* ; Dedoussis, G.* ; Gonidakis, F.* ; Thanopoulou, A.* ; Tentolouris, N.* ; Tsezou, A.* ; Zeggini, E.

Evidence for genetic contribution to the increased risk of type 2 diabetes in schizophrenia.

Transl. Psychiatry 8:252 (2018)
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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
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 2158-3188
e-ISSN 2158-3188
Journal Translational Psychiatry
Quellenangaben Volume: 8, Issue: 1, Pages: , Article Number: 252 Supplement: ,
Publisher Nature Publishing Group
Publishing Place 75 Varick St, 9th Flr, New York, Ny 10013-1917 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-506700-001
DOI 10.1038/s41398-018-0304-6
WOS ID WOS:000451122300001
Scopus ID 85057126988
PubMed ID 30470734
Erfassungsdatum 2018-12-06
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