Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci

Trine Folseraas; Espen Melum; Philipp Rausch; Brian D. Juran; Eva Ellinghaus; Alexey Shiryaev; Jon K. Laerdahl; David Ellinghaus; Christoph Schramm; Tobias J. Weismueller; Daniel Nils Gotthard; Johannes Roksund Hov; Ole Petter Clausen; Rinse K. Weersma; Marcel Janse; Kirsten Muri Boberg; Einar Bjornsson; Hanns-Ulrich Marschall; Isabelle Cleynen; Philip Rosenstiel; Kristian Holm; Andreas Teufel; Christian Rust; Christian Gieger; H-Erich Wichmann; Annika Bergquist; Euijung Ryu; Cyriel Y. Ponsioen; Heiko Runz; Martina Sterneck; Severine Vermeire; Ulrich Beuers; Cisca Wijmenga; Erik Schrumpf; Michael P. Manns; Konstantinos N. Lazaridis; Stefan Schreiber; John F. Baines; Andre Franke; Tom H. Karlsen

doi:10.1016/j.jhep.2012.03.031

Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci

Trine Folseraas, Espen Melum, Philipp Rausch, Brian D. Juran, Eva Ellinghaus, Alexey Shiryaev, Jon K. Laerdahl, David Ellinghaus, Christoph Schramm, Tobias J. Weismueller, Daniel Nils Gotthard, Johannes Roksund Hov, Ole Petter Clausen, Rinse K. Weersma, Marcel Janse, Kirsten Muri Boberg, Einar Bjornsson, Hanns-Ulrich Marschall, Isabelle Cleynen, Philip RosenstielKristian Holm, Andreas Teufel, Christian Rust, Christian Gieger, H-Erich Wichmann, Annika Bergquist, Euijung Ryu, Cyriel Y. Ponsioen, Heiko Runz, Martina Sterneck, Severine Vermeire, Ulrich Beuers, Cisca Wijmenga, Erik Schrumpf, Michael P. Manns, Konstantinos N. Lazaridis, Stefan Schreiber, John F. Baines, Andre Franke, Tom H. Karlsen^*

^*Corresponding author for this work

Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Research output: Contribution to journal › Article › Academic › peer-review

153 Citations (Scopus)

Abstract

Background & Aims: A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on,a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS).

Methods: We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing.

Results: Seventeen SNPs representing 12 distinct genetic loci achieved nominal significance (p(replication)

Conclusions: We identify multiple new PSC risk loci by extended analysis of a PSC GWAS. FUT2 genotype needs to be taken into account when assessing the influence of microbiota on biliary pathology in PSC. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	366-375
Number of pages	10
Journal	Journal of Hepatology
Volume	57
Issue number	2
DOIs	https://doi.org/10.1016/j.jhep.2012.03.031
Publication status	Published - Aug-2012

Keywords

Primary sclerosing cholangitis
Genome-wide association study
Single nucleotide polymorphism
Immunogenetics
T-LYMPHOCYTE ATTENUATOR
NON-SECRETOR STATUS
SUSCEPTIBILITY LOCI
B-LYMPHOCYTE
BLOOD-GROUP
FUT2
POPULATION
DISEASES
GENE
METAANALYSIS

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10.1016/j.jhep.2012.03.031

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Folseraas, T., Melum, E., Rausch, P., Juran, B. D., Ellinghaus, E., Shiryaev, A., Laerdahl, J. K., Ellinghaus, D., Schramm, C., Weismueller, T. J., Gotthard, D. N., Hov, J. R., Clausen, O. P., Weersma, R. K., Janse, M., Boberg, K. M., Bjornsson, E., Marschall, H-U., Cleynen, I., ... Karlsen, T. H. (2012). Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. Journal of Hepatology, 57(2), 366-375. https://doi.org/10.1016/j.jhep.2012.03.031

Folseraas, Trine ; Melum, Espen ; Rausch, Philipp ; Juran, Brian D. ; Ellinghaus, Eva ; Shiryaev, Alexey ; Laerdahl, Jon K. ; Ellinghaus, David ; Schramm, Christoph ; Weismueller, Tobias J. ; Gotthard, Daniel Nils ; Hov, Johannes Roksund ; Clausen, Ole Petter ; Weersma, Rinse K. ; Janse, Marcel ; Boberg, Kirsten Muri ; Bjornsson, Einar ; Marschall, Hanns-Ulrich ; Cleynen, Isabelle ; Rosenstiel, Philip ; Holm, Kristian ; Teufel, Andreas ; Rust, Christian ; Gieger, Christian ; Wichmann, H-Erich ; Bergquist, Annika ; Ryu, Euijung ; Ponsioen, Cyriel Y. ; Runz, Heiko ; Sterneck, Martina ; Vermeire, Severine ; Beuers, Ulrich ; Wijmenga, Cisca ; Schrumpf, Erik ; Manns, Michael P. ; Lazaridis, Konstantinos N. ; Schreiber, Stefan ; Baines, John F. ; Franke, Andre ; Karlsen, Tom H. / Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. In: Journal of Hepatology. 2012 ; Vol. 57, No. 2. pp. 366-375.

@article{40aef1f67ed348d29bee614f6554866a,

title = "Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci",

abstract = "Background & Aims: A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on,a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS).Methods: We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing.Results: Seventeen SNPs representing 12 distinct genetic loci achieved nominal significance (p(replication)Conclusions: We identify multiple new PSC risk loci by extended analysis of a PSC GWAS. FUT2 genotype needs to be taken into account when assessing the influence of microbiota on biliary pathology in PSC. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",

keywords = "Primary sclerosing cholangitis, Genome-wide association study, Single nucleotide polymorphism, Immunogenetics, T-LYMPHOCYTE ATTENUATOR, NON-SECRETOR STATUS, SUSCEPTIBILITY LOCI, B-LYMPHOCYTE, BLOOD-GROUP, FUT2, POPULATION, DISEASES, GENE, METAANALYSIS",

author = "Trine Folseraas and Espen Melum and Philipp Rausch and Juran, {Brian D.} and Eva Ellinghaus and Alexey Shiryaev and Laerdahl, {Jon K.} and David Ellinghaus and Christoph Schramm and Weismueller, {Tobias J.} and Gotthard, {Daniel Nils} and Hov, {Johannes Roksund} and Clausen, {Ole Petter} and Weersma, {Rinse K.} and Marcel Janse and Boberg, {Kirsten Muri} and Einar Bjornsson and Hanns-Ulrich Marschall and Isabelle Cleynen and Philip Rosenstiel and Kristian Holm and Andreas Teufel and Christian Rust and Christian Gieger and H-Erich Wichmann and Annika Bergquist and Euijung Ryu and Ponsioen, {Cyriel Y.} and Heiko Runz and Martina Sterneck and Severine Vermeire and Ulrich Beuers and Cisca Wijmenga and Erik Schrumpf and Manns, {Michael P.} and Lazaridis, {Konstantinos N.} and Stefan Schreiber and Baines, {John F.} and Andre Franke and Karlsen, {Tom H.}",

year = "2012",

month = aug,

doi = "10.1016/j.jhep.2012.03.031",

language = "English",

volume = "57",

pages = "366--375",

journal = "Journal of Hepatology",

issn = "0168-8278",

publisher = "ELSEVIER SCIENCE BV",

number = "2",

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Folseraas, T, Melum, E, Rausch, P, Juran, BD, Ellinghaus, E, Shiryaev, A, Laerdahl, JK, Ellinghaus, D, Schramm, C, Weismueller, TJ, Gotthard, DN, Hov, JR, Clausen, OP, Weersma, RK, Janse, M, Boberg, KM, Bjornsson, E, Marschall, H-U, Cleynen, I, Rosenstiel, P, Holm, K, Teufel, A, Rust, C, Gieger, C, Wichmann, H-E, Bergquist, A, Ryu, E, Ponsioen, CY, Runz, H, Sterneck, M, Vermeire, S, Beuers, U, Wijmenga, C, Schrumpf, E, Manns, MP, Lazaridis, KN, Schreiber, S, Baines, JF, Franke, A & Karlsen, TH 2012, 'Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci', Journal of Hepatology, vol. 57, no. 2, pp. 366-375. https://doi.org/10.1016/j.jhep.2012.03.031

Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci. / Folseraas, Trine; Melum, Espen; Rausch, Philipp; Juran, Brian D.; Ellinghaus, Eva; Shiryaev, Alexey; Laerdahl, Jon K.; Ellinghaus, David; Schramm, Christoph; Weismueller, Tobias J.; Gotthard, Daniel Nils; Hov, Johannes Roksund; Clausen, Ole Petter; Weersma, Rinse K.; Janse, Marcel; Boberg, Kirsten Muri; Bjornsson, Einar; Marschall, Hanns-Ulrich; Cleynen, Isabelle; Rosenstiel, Philip; Holm, Kristian; Teufel, Andreas; Rust, Christian; Gieger, Christian; Wichmann, H-Erich; Bergquist, Annika; Ryu, Euijung; Ponsioen, Cyriel Y.; Runz, Heiko; Sterneck, Martina; Vermeire, Severine; Beuers, Ulrich; Wijmenga, Cisca; Schrumpf, Erik; Manns, Michael P.; Lazaridis, Konstantinos N.; Schreiber, Stefan; Baines, John F.; Franke, Andre; Karlsen, Tom H.

In: Journal of Hepatology, Vol. 57, No. 2, 08.2012, p. 366-375.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci

AU - Folseraas, Trine

AU - Melum, Espen

AU - Rausch, Philipp

AU - Juran, Brian D.

AU - Ellinghaus, Eva

AU - Shiryaev, Alexey

AU - Laerdahl, Jon K.

AU - Ellinghaus, David

AU - Schramm, Christoph

AU - Weismueller, Tobias J.

AU - Gotthard, Daniel Nils

AU - Hov, Johannes Roksund

AU - Clausen, Ole Petter

AU - Weersma, Rinse K.

AU - Janse, Marcel

AU - Boberg, Kirsten Muri

AU - Bjornsson, Einar

AU - Marschall, Hanns-Ulrich

AU - Cleynen, Isabelle

AU - Rosenstiel, Philip

AU - Holm, Kristian

AU - Teufel, Andreas

AU - Rust, Christian

AU - Gieger, Christian

AU - Wichmann, H-Erich

AU - Bergquist, Annika

AU - Ryu, Euijung

AU - Ponsioen, Cyriel Y.

AU - Runz, Heiko

AU - Sterneck, Martina

AU - Vermeire, Severine

AU - Beuers, Ulrich

AU - Wijmenga, Cisca

AU - Schrumpf, Erik

AU - Manns, Michael P.

AU - Lazaridis, Konstantinos N.

AU - Schreiber, Stefan

AU - Baines, John F.

AU - Franke, Andre

AU - Karlsen, Tom H.

PY - 2012/8

Y1 - 2012/8

N2 - Background & Aims: A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on,a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS).Methods: We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing.Results: Seventeen SNPs representing 12 distinct genetic loci achieved nominal significance (p(replication)Conclusions: We identify multiple new PSC risk loci by extended analysis of a PSC GWAS. FUT2 genotype needs to be taken into account when assessing the influence of microbiota on biliary pathology in PSC. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

AB - Background & Aims: A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on,a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS).Methods: We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing.Results: Seventeen SNPs representing 12 distinct genetic loci achieved nominal significance (p(replication)Conclusions: We identify multiple new PSC risk loci by extended analysis of a PSC GWAS. FUT2 genotype needs to be taken into account when assessing the influence of microbiota on biliary pathology in PSC. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

KW - Primary sclerosing cholangitis

KW - Genome-wide association study

KW - Single nucleotide polymorphism

KW - Immunogenetics

KW - T-LYMPHOCYTE ATTENUATOR

KW - NON-SECRETOR STATUS

KW - SUSCEPTIBILITY LOCI

KW - B-LYMPHOCYTE

KW - BLOOD-GROUP

KW - FUT2

KW - POPULATION

KW - DISEASES

KW - GENE

KW - METAANALYSIS

U2 - 10.1016/j.jhep.2012.03.031

DO - 10.1016/j.jhep.2012.03.031

M3 - Article

VL - 57

SP - 366

EP - 375

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 2

ER -