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Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9.

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Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9. / Janse, Marcel; Lamberts, Laetitia E; Franke, Lude; Raychaudhuri, Soumya; Ellinghaus, Eva; Kirsten, Muri Boberg; Melum, Espen; Folseraas, Trine; Schrumpf, Erik; Bergquist, Annika; Björnsson, Einar; Fu, Jingyuan; Harm, Jan Westra; Groen, Harry J M; Fehrmann, Rudolf S N; Smolonska, Joanna; Berg, van den; Leonard, H; Ophoff, Roel A; Porte, Robert J; Weismüller, Tobias J; Schramm, Christoph; Sterneck, Martina; Sterneck, Martina; Günther, Rainer; Braun, Felix; Vermeire, Severine; Henckaerts, Liesbet; Wijmenga, Cisca; Ponsioen, Cyriel Y; Schreiber, Stefan; Karlsen, Tom H; Franke, Andre; Weersma, Rinse K.

In: HEPATOLOGY, Vol. 53, No. 6, 6, 2011, p. 1977-1985.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Janse, M, Lamberts, LE, Franke, L, Raychaudhuri, S, Ellinghaus, E, Kirsten, MB, Melum, E, Folseraas, T, Schrumpf, E, Bergquist, A, Björnsson, E, Fu, J, Harm, JW, Groen, HJM, Fehrmann, RSN, Smolonska, J, Berg, VD, Leonard, H, Ophoff, RA, Porte, RJ, Weismüller, TJ, Schramm, C, Sterneck, M, Sterneck, M, Günther, R, Braun, F, Vermeire, S, Henckaerts, L, Wijmenga, C, Ponsioen, CY, Schreiber, S, Karlsen, TH, Franke, A & Weersma, RK 2011, 'Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9.', HEPATOLOGY, vol. 53, no. 6, 6, pp. 1977-1985. <http://www.ncbi.nlm.nih.gov/pubmed/21425313?dopt=Citation>

APA

Janse, M., Lamberts, L. E., Franke, L., Raychaudhuri, S., Ellinghaus, E., Kirsten, M. B., Melum, E., Folseraas, T., Schrumpf, E., Bergquist, A., Björnsson, E., Fu, J., Harm, J. W., Groen, H. J. M., Fehrmann, R. S. N., Smolonska, J., Berg, V. D., Leonard, H., Ophoff, R. A., ... Weersma, R. K. (2011). Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9. HEPATOLOGY, 53(6), 1977-1985. [6]. http://www.ncbi.nlm.nih.gov/pubmed/21425313?dopt=Citation

Vancouver

Janse M, Lamberts LE, Franke L, Raychaudhuri S, Ellinghaus E, Kirsten MB et al. Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9. HEPATOLOGY. 2011;53(6):1977-1985. 6.

Bibtex

@article{22e5e4debbb04b8cae43e18e58a9ee17,
title = "Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9.",
abstract = "Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Both environmental and genetic factors contribute to its pathogenesis. To further clarify its genetic background, we investigated susceptibility loci recently identified for ulcerative colitis (UC) in a large cohort of 1,186 PSC patients and 1,748 controls. Single nucleotide polymorphisms (SNPs) tagging 13 UC susceptibility loci were initially genotyped in 854 PSC patients and 1,491 controls from Benelux (331 cases, 735 controls), Germany (265 cases, 368 controls), and Scandinavia (258 cases, 388 controls). Subsequently, a joint analysis was performed with an independent second Scandinavian cohort (332 cases, 257 controls). SNPs at chromosomes 2p16 (P-value 4.12 × 10(-4) ), 4q27 (P-value 4.10 × 10(-5) ), and 9q34 (P-value 8.41 × 10(-4) ) were associated with PSC in the joint analysis after correcting for multiple testing. In PSC patients without inflammatory bowel disease (IBD), SNPs at 4q27 and 9q34 were nominally associated (P < 0.05). We applied additional in silico analyses to identify likely candidate genes at PSC susceptibility loci. To identify nonrandom, evidence-based links we used GRAIL (Gene Relationships Across Implicated Loci) analysis showing interconnectivity between genes in six out of in total nine PSC-associated regions. Expression quantitative trait analysis from 1,469 Dutch and UK individuals demonstrated that five out of nine SNPs had an effect on cis-gene expression. These analyses prioritized IL2, CARD9, and REL as novel candidates. CONCLUSION: We have identified three UC susceptibility loci to be associated with PSC, harboring the putative candidate genes REL, IL2, and CARD9. These results add to the scarce knowledge on the genetic background of PSC and imply an important role for both innate and adaptive immunological factors.",
keywords = "Germany, Humans, Cohort Studies, Genotype, Alleles, Case-Control Studies, Netherlands, Quantitative Trait Loci, CARD Signaling Adaptor Proteins/*genetics/physiology, Cholangitis, Sclerosing/ethnology/genetics, Colitis, Ulcerative/ethnology/*genetics, Genetic Predisposition to Disease/ethnology/*genetics, Interleukin-2/*genetics/physiology, Polymorphism, Single Nucleotide/genetics, Proto-Oncogene Proteins c-rel/*genetics/physiology, Scandinavia, Germany, Humans, Cohort Studies, Genotype, Alleles, Case-Control Studies, Netherlands, Quantitative Trait Loci, CARD Signaling Adaptor Proteins/*genetics/physiology, Cholangitis, Sclerosing/ethnology/genetics, Colitis, Ulcerative/ethnology/*genetics, Genetic Predisposition to Disease/ethnology/*genetics, Interleukin-2/*genetics/physiology, Polymorphism, Single Nucleotide/genetics, Proto-Oncogene Proteins c-rel/*genetics/physiology, Scandinavia",
author = "Marcel Janse and Lamberts, {Laetitia E} and Lude Franke and Soumya Raychaudhuri and Eva Ellinghaus and Kirsten, {Muri Boberg} and Espen Melum and Trine Folseraas and Erik Schrumpf and Annika Bergquist and Einar Bj{\"o}rnsson and Jingyuan Fu and Harm, {Jan Westra} and Groen, {Harry J M} and Fehrmann, {Rudolf S N} and Joanna Smolonska and Berg, {van den} and H Leonard and Ophoff, {Roel A} and Porte, {Robert J} and Weism{\"u}ller, {Tobias J} and Christoph Schramm and Martina Sterneck and Martina Sterneck and Rainer G{\"u}nther and Felix Braun and Severine Vermeire and Liesbet Henckaerts and Cisca Wijmenga and Ponsioen, {Cyriel Y} and Stefan Schreiber and Karlsen, {Tom H} and Andre Franke and Weersma, {Rinse K}",
year = "2011",
language = "English",
volume = "53",
pages = "1977--1985",
journal = "HEPATOLOGY",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

RIS

TY - JOUR

T1 - Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9.

AU - Janse, Marcel

AU - Lamberts, Laetitia E

AU - Franke, Lude

AU - Raychaudhuri, Soumya

AU - Ellinghaus, Eva

AU - Kirsten, Muri Boberg

AU - Melum, Espen

AU - Folseraas, Trine

AU - Schrumpf, Erik

AU - Bergquist, Annika

AU - Björnsson, Einar

AU - Fu, Jingyuan

AU - Harm, Jan Westra

AU - Groen, Harry J M

AU - Fehrmann, Rudolf S N

AU - Smolonska, Joanna

AU - Berg, van den

AU - Leonard, H

AU - Ophoff, Roel A

AU - Porte, Robert J

AU - Weismüller, Tobias J

AU - Schramm, Christoph

AU - Sterneck, Martina

AU - Sterneck, Martina

AU - Günther, Rainer

AU - Braun, Felix

AU - Vermeire, Severine

AU - Henckaerts, Liesbet

AU - Wijmenga, Cisca

AU - Ponsioen, Cyriel Y

AU - Schreiber, Stefan

AU - Karlsen, Tom H

AU - Franke, Andre

AU - Weersma, Rinse K

PY - 2011

Y1 - 2011

N2 - Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Both environmental and genetic factors contribute to its pathogenesis. To further clarify its genetic background, we investigated susceptibility loci recently identified for ulcerative colitis (UC) in a large cohort of 1,186 PSC patients and 1,748 controls. Single nucleotide polymorphisms (SNPs) tagging 13 UC susceptibility loci were initially genotyped in 854 PSC patients and 1,491 controls from Benelux (331 cases, 735 controls), Germany (265 cases, 368 controls), and Scandinavia (258 cases, 388 controls). Subsequently, a joint analysis was performed with an independent second Scandinavian cohort (332 cases, 257 controls). SNPs at chromosomes 2p16 (P-value 4.12 × 10(-4) ), 4q27 (P-value 4.10 × 10(-5) ), and 9q34 (P-value 8.41 × 10(-4) ) were associated with PSC in the joint analysis after correcting for multiple testing. In PSC patients without inflammatory bowel disease (IBD), SNPs at 4q27 and 9q34 were nominally associated (P < 0.05). We applied additional in silico analyses to identify likely candidate genes at PSC susceptibility loci. To identify nonrandom, evidence-based links we used GRAIL (Gene Relationships Across Implicated Loci) analysis showing interconnectivity between genes in six out of in total nine PSC-associated regions. Expression quantitative trait analysis from 1,469 Dutch and UK individuals demonstrated that five out of nine SNPs had an effect on cis-gene expression. These analyses prioritized IL2, CARD9, and REL as novel candidates. CONCLUSION: We have identified three UC susceptibility loci to be associated with PSC, harboring the putative candidate genes REL, IL2, and CARD9. These results add to the scarce knowledge on the genetic background of PSC and imply an important role for both innate and adaptive immunological factors.

AB - Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Both environmental and genetic factors contribute to its pathogenesis. To further clarify its genetic background, we investigated susceptibility loci recently identified for ulcerative colitis (UC) in a large cohort of 1,186 PSC patients and 1,748 controls. Single nucleotide polymorphisms (SNPs) tagging 13 UC susceptibility loci were initially genotyped in 854 PSC patients and 1,491 controls from Benelux (331 cases, 735 controls), Germany (265 cases, 368 controls), and Scandinavia (258 cases, 388 controls). Subsequently, a joint analysis was performed with an independent second Scandinavian cohort (332 cases, 257 controls). SNPs at chromosomes 2p16 (P-value 4.12 × 10(-4) ), 4q27 (P-value 4.10 × 10(-5) ), and 9q34 (P-value 8.41 × 10(-4) ) were associated with PSC in the joint analysis after correcting for multiple testing. In PSC patients without inflammatory bowel disease (IBD), SNPs at 4q27 and 9q34 were nominally associated (P < 0.05). We applied additional in silico analyses to identify likely candidate genes at PSC susceptibility loci. To identify nonrandom, evidence-based links we used GRAIL (Gene Relationships Across Implicated Loci) analysis showing interconnectivity between genes in six out of in total nine PSC-associated regions. Expression quantitative trait analysis from 1,469 Dutch and UK individuals demonstrated that five out of nine SNPs had an effect on cis-gene expression. These analyses prioritized IL2, CARD9, and REL as novel candidates. CONCLUSION: We have identified three UC susceptibility loci to be associated with PSC, harboring the putative candidate genes REL, IL2, and CARD9. These results add to the scarce knowledge on the genetic background of PSC and imply an important role for both innate and adaptive immunological factors.

KW - Germany

KW - Humans

KW - Cohort Studies

KW - Genotype

KW - Alleles

KW - Case-Control Studies

KW - Netherlands

KW - Quantitative Trait Loci

KW - CARD Signaling Adaptor Proteins/genetics/physiology

KW - Cholangitis, Sclerosing/ethnology/genetics

KW - Colitis, Ulcerative/ethnology/genetics

KW - Genetic Predisposition to Disease/ethnology/genetics

KW - Interleukin-2/genetics/physiology

KW - Polymorphism, Single Nucleotide/genetics

KW - Proto-Oncogene Proteins c-rel/genetics/physiology

KW - Scandinavia

KW - Germany

KW - Humans

KW - Cohort Studies

KW - Genotype

KW - Alleles

KW - Case-Control Studies

KW - Netherlands

KW - Quantitative Trait Loci

KW - CARD Signaling Adaptor Proteins/genetics/physiology

KW - Cholangitis, Sclerosing/ethnology/genetics

KW - Colitis, Ulcerative/ethnology/genetics

KW - Genetic Predisposition to Disease/ethnology/genetics

KW - Interleukin-2/genetics/physiology

KW - Polymorphism, Single Nucleotide/genetics

KW - Proto-Oncogene Proteins c-rel/genetics/physiology

KW - Scandinavia

M3 - SCORING: Journal article

VL - 53

SP - 1977

EP - 1985

JO - HEPATOLOGY

JF - HEPATOLOGY

SN - 0270-9139

IS - 6

M1 - 6

ER -