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Cross-tissue transcriptome-wide association studies identify susceptibility genes shared between schizophrenia and inflammatory bowel disease

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Cross-tissue transcriptome-wide association studies identify susceptibility genes shared between schizophrenia and inflammatory bowel disease. / Uellendahl-Werth, Florian; Maj, Carlo; Borisov, Oleg; Juzenas, Simonas; Wacker, Eike Matthias; Jørgensen, Isabella Friis; Steiert, Tim Alexander; Bej, Saptarshi; Krawitz, Peter; Hoffmann, Per; Schramm, Christoph; Wolkenhauer, Olaf; Banasik, Karina; Brunak, Søren; Schreiber, Stefan; Karlsen, Tom Hemming; Degenhardt, Franziska; Nöthen, Markus; Franke, Andre; Folseraas, Trine; Ellinghaus, David.

in: COMMUN BIOL, Jahrgang 5, Nr. 1, 80, 20.01.2022.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Uellendahl-Werth, F, Maj, C, Borisov, O, Juzenas, S, Wacker, EM, Jørgensen, IF, Steiert, TA, Bej, S, Krawitz, P, Hoffmann, P, Schramm, C, Wolkenhauer, O, Banasik, K, Brunak, S, Schreiber, S, Karlsen, TH, Degenhardt, F, Nöthen, M, Franke, A, Folseraas, T & Ellinghaus, D 2022, 'Cross-tissue transcriptome-wide association studies identify susceptibility genes shared between schizophrenia and inflammatory bowel disease', COMMUN BIOL, Jg. 5, Nr. 1, 80. https://doi.org/10.1038/s42003-022-03031-6

APA

Uellendahl-Werth, F., Maj, C., Borisov, O., Juzenas, S., Wacker, E. M., Jørgensen, I. F., Steiert, T. A., Bej, S., Krawitz, P., Hoffmann, P., Schramm, C., Wolkenhauer, O., Banasik, K., Brunak, S., Schreiber, S., Karlsen, T. H., Degenhardt, F., Nöthen, M., Franke, A., ... Ellinghaus, D. (2022). Cross-tissue transcriptome-wide association studies identify susceptibility genes shared between schizophrenia and inflammatory bowel disease. COMMUN BIOL, 5(1), [80]. https://doi.org/10.1038/s42003-022-03031-6

Vancouver

Uellendahl-Werth F, Maj C, Borisov O, Juzenas S, Wacker EM, Jørgensen IF et al. Cross-tissue transcriptome-wide association studies identify susceptibility genes shared between schizophrenia and inflammatory bowel disease. COMMUN BIOL. 2022 Jan 20;5(1). 80. https://doi.org/10.1038/s42003-022-03031-6

Bibtex

@article{b994a85c1dbc4a74bee02fa0d8617e33,
title = "Cross-tissue transcriptome-wide association studies identify susceptibility genes shared between schizophrenia and inflammatory bowel disease",
abstract = "Genetic correlations and an increased incidence of psychiatric disorders in inflammatory-bowel disease have been reported, but shared molecular mechanisms are unknown. We performed cross-tissue and multiple-gene conditioned transcriptome-wide association studies for 23 tissues of the gut-brain-axis using genome-wide association studies data sets (total 180,592 patients) for Crohn's disease, ulcerative colitis, primary sclerosing cholangitis, schizophrenia, bipolar disorder, major depressive disorder and attention-deficit/hyperactivity disorder. We identified NR5A2, SATB2, and PPP3CA (encoding a target for calcineurin inhibitors in refractory ulcerative colitis) as shared susceptibility genes with transcriptome-wide significance both for Crohn's disease, ulcerative colitis and schizophrenia, largely explaining fine-mapped association signals at nearby genome-wide association study susceptibility loci. Analysis of bulk and single-cell RNA-sequencing data showed that PPP3CA expression was strongest in neurons and in enteroendocrine and Paneth-like cells of the ileum, colon, and rectum, indicating a possible link to the gut-brain-axis. PPP3CA together with three further suggestive loci can be linked to calcineurin-related signaling pathways such as NFAT activation or Wnt.",
author = "Florian Uellendahl-Werth and Carlo Maj and Oleg Borisov and Simonas Juzenas and Wacker, {Eike Matthias} and J{\o}rgensen, {Isabella Friis} and Steiert, {Tim Alexander} and Saptarshi Bej and Peter Krawitz and Per Hoffmann and Christoph Schramm and Olaf Wolkenhauer and Karina Banasik and S{\o}ren Brunak and Stefan Schreiber and Karlsen, {Tom Hemming} and Franziska Degenhardt and Markus N{\"o}then and Andre Franke and Trine Folseraas and David Ellinghaus",
note = "{\textcopyright} 2022. The Author(s).",
year = "2022",
month = jan,
day = "20",
doi = "10.1038/s42003-022-03031-6",
language = "English",
volume = "5",
journal = "COMMUN BIOL",
issn = "2399-3642",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Cross-tissue transcriptome-wide association studies identify susceptibility genes shared between schizophrenia and inflammatory bowel disease

AU - Uellendahl-Werth, Florian

AU - Maj, Carlo

AU - Borisov, Oleg

AU - Juzenas, Simonas

AU - Wacker, Eike Matthias

AU - Jørgensen, Isabella Friis

AU - Steiert, Tim Alexander

AU - Bej, Saptarshi

AU - Krawitz, Peter

AU - Hoffmann, Per

AU - Schramm, Christoph

AU - Wolkenhauer, Olaf

AU - Banasik, Karina

AU - Brunak, Søren

AU - Schreiber, Stefan

AU - Karlsen, Tom Hemming

AU - Degenhardt, Franziska

AU - Nöthen, Markus

AU - Franke, Andre

AU - Folseraas, Trine

AU - Ellinghaus, David

N1 - © 2022. The Author(s).

PY - 2022/1/20

Y1 - 2022/1/20

N2 - Genetic correlations and an increased incidence of psychiatric disorders in inflammatory-bowel disease have been reported, but shared molecular mechanisms are unknown. We performed cross-tissue and multiple-gene conditioned transcriptome-wide association studies for 23 tissues of the gut-brain-axis using genome-wide association studies data sets (total 180,592 patients) for Crohn's disease, ulcerative colitis, primary sclerosing cholangitis, schizophrenia, bipolar disorder, major depressive disorder and attention-deficit/hyperactivity disorder. We identified NR5A2, SATB2, and PPP3CA (encoding a target for calcineurin inhibitors in refractory ulcerative colitis) as shared susceptibility genes with transcriptome-wide significance both for Crohn's disease, ulcerative colitis and schizophrenia, largely explaining fine-mapped association signals at nearby genome-wide association study susceptibility loci. Analysis of bulk and single-cell RNA-sequencing data showed that PPP3CA expression was strongest in neurons and in enteroendocrine and Paneth-like cells of the ileum, colon, and rectum, indicating a possible link to the gut-brain-axis. PPP3CA together with three further suggestive loci can be linked to calcineurin-related signaling pathways such as NFAT activation or Wnt.

AB - Genetic correlations and an increased incidence of psychiatric disorders in inflammatory-bowel disease have been reported, but shared molecular mechanisms are unknown. We performed cross-tissue and multiple-gene conditioned transcriptome-wide association studies for 23 tissues of the gut-brain-axis using genome-wide association studies data sets (total 180,592 patients) for Crohn's disease, ulcerative colitis, primary sclerosing cholangitis, schizophrenia, bipolar disorder, major depressive disorder and attention-deficit/hyperactivity disorder. We identified NR5A2, SATB2, and PPP3CA (encoding a target for calcineurin inhibitors in refractory ulcerative colitis) as shared susceptibility genes with transcriptome-wide significance both for Crohn's disease, ulcerative colitis and schizophrenia, largely explaining fine-mapped association signals at nearby genome-wide association study susceptibility loci. Analysis of bulk and single-cell RNA-sequencing data showed that PPP3CA expression was strongest in neurons and in enteroendocrine and Paneth-like cells of the ileum, colon, and rectum, indicating a possible link to the gut-brain-axis. PPP3CA together with three further suggestive loci can be linked to calcineurin-related signaling pathways such as NFAT activation or Wnt.

U2 - 10.1038/s42003-022-03031-6

DO - 10.1038/s42003-022-03031-6

M3 - SCORING: Journal article

C2 - 35058554

VL - 5

JO - COMMUN BIOL

JF - COMMUN BIOL

SN - 2399-3642

IS - 1

M1 - 80

ER -