Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

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Standard

Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. / Ellinghaus, David; Jostins, Luke; Spain, Sarah L; Cortes, Adrian; Bethune, Jörn; Han, Buhm; Park, Yu Rang; Raychaudhuri, Soumya; Pouget, Jennie G; Hübenthal, Matthias; Folseraas, Trine; Wang, Yunpeng; Esko, Tonu; Metspalu, Andres; Westra, Harm-Jan; Franke, Lude; Pers, Tune H; Weersma, Rinse K; Collij, Valerie; D'Amato, Mauro; Halfvarson, Jonas; Jensen, Anders Boeck; Lieb, Wolfgang; Degenhardt, Franziska; Forstner, Andreas J; Hofmann, Andrea; Schreiber, Stefan; Mrowietz, Ulrich; Juran, Brian D; Lazaridis, Konstantinos N; Brunak, Søren; Dale, Anders M; Trembath, Richard C; Weidinger, Stephan; Weichenthal, Michael; Ellinghaus, Eva; Elder, James T; Barker, Jonathan N W N; Andreassen, Ole A; McGovern, Dermot P; Karlsen, Tom H; Barrett, Jeffrey C; Parkes, Miles; Brown, Matthew A; Franke, Andre; International IBD Genetics Consortium (IIBDGC).

In: Nature Genetics, Vol. 48, No. 5, 05.2016, p. 510-521.

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

Harvard

Ellinghaus, D, Jostins, L, Spain, SL, Cortes, A, Bethune, J, Han, B, Park, YR, Raychaudhuri, S, Pouget, JG, Hübenthal, M, Folseraas, T, Wang, Y, Esko, T, Metspalu, A, Westra, H-J, Franke, L, Pers, TH, Weersma, RK, Collij, V, D'Amato, M, Halfvarson, J, Jensen, AB, Lieb, W, Degenhardt, F, Forstner, AJ, Hofmann, A, Schreiber, S, Mrowietz, U, Juran, BD, Lazaridis, KN, Brunak, S, Dale, AM, Trembath, RC, Weidinger, S, Weichenthal, M, Ellinghaus, E, Elder, JT, Barker, JNWN, Andreassen, OA, McGovern, DP, Karlsen, TH, Barrett, JC, Parkes, M, Brown, MA, Franke, A & International IBD Genetics Consortium (IIBDGC) 2016, 'Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci', Nature Genetics, vol. 48, no. 5, pp. 510-521. https://doi.org/10.1038/ng.3528

APA

Ellinghaus, D., Jostins, L., Spain, S. L., Cortes, A., Bethune, J., Han, B., Park, Y. R., Raychaudhuri, S., Pouget, J. G., Hübenthal, M., Folseraas, T., Wang, Y., Esko, T., Metspalu, A., Westra, H-J., Franke, L., Pers, T. H., Weersma, R. K., Collij, V., ... International IBD Genetics Consortium (IIBDGC) (2016). Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nature Genetics, 48(5), 510-521. https://doi.org/10.1038/ng.3528

Vancouver

Ellinghaus D, Jostins L, Spain SL, Cortes A, Bethune J, Han B et al. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nature Genetics. 2016 May;48(5):510-521. https://doi.org/10.1038/ng.3528

Author

Ellinghaus, David ; Jostins, Luke ; Spain, Sarah L ; Cortes, Adrian ; Bethune, Jörn ; Han, Buhm ; Park, Yu Rang ; Raychaudhuri, Soumya ; Pouget, Jennie G ; Hübenthal, Matthias ; Folseraas, Trine ; Wang, Yunpeng ; Esko, Tonu ; Metspalu, Andres ; Westra, Harm-Jan ; Franke, Lude ; Pers, Tune H ; Weersma, Rinse K ; Collij, Valerie ; D'Amato, Mauro ; Halfvarson, Jonas ; Jensen, Anders Boeck ; Lieb, Wolfgang ; Degenhardt, Franziska ; Forstner, Andreas J ; Hofmann, Andrea ; Schreiber, Stefan ; Mrowietz, Ulrich ; Juran, Brian D ; Lazaridis, Konstantinos N ; Brunak, Søren ; Dale, Anders M ; Trembath, Richard C ; Weidinger, Stephan ; Weichenthal, Michael ; Ellinghaus, Eva ; Elder, James T ; Barker, Jonathan N W N ; Andreassen, Ole A ; McGovern, Dermot P ; Karlsen, Tom H ; Barrett, Jeffrey C ; Parkes, Miles ; Brown, Matthew A ; Franke, Andre ; International IBD Genetics Consortium (IIBDGC). / Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. In: Nature Genetics. 2016 ; Vol. 48, No. 5. pp. 510-521.

Bibtex

@article{9820b945e08448b185f31c905bd01216,
title = "Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci",
abstract = "We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.",
author = "David Ellinghaus and Luke Jostins and Spain, {Sarah L} and Adrian Cortes and J{\"o}rn Bethune and Buhm Han and Park, {Yu Rang} and Soumya Raychaudhuri and Pouget, {Jennie G} and Matthias H{\"u}benthal and Trine Folseraas and Yunpeng Wang and Tonu Esko and Andres Metspalu and Harm-Jan Westra and Lude Franke and Pers, {Tune H} and Weersma, {Rinse K} and Valerie Collij and Mauro D'Amato and Jonas Halfvarson and Jensen, {Anders Boeck} and Wolfgang Lieb and Franziska Degenhardt and Forstner, {Andreas J} and Andrea Hofmann and Stefan Schreiber and Ulrich Mrowietz and Juran, {Brian D} and Lazaridis, {Konstantinos N} and S{\o}ren Brunak and Dale, {Anders M} and Trembath, {Richard C} and Stephan Weidinger and Michael Weichenthal and Eva Ellinghaus and Elder, {James T} and Barker, {Jonathan N W N} and Andreassen, {Ole A} and McGovern, {Dermot P} and Karlsen, {Tom H} and Barrett, {Jeffrey C} and Miles Parkes and Brown, {Matthew A} and Andre Franke and {International IBD Genetics Consortium (IIBDGC)}",
year = "2016",
month = may,
doi = "10.1038/ng.3528",
language = "English",
volume = "48",
pages = "510--521",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "5",

}

RIS

TY - JOUR

T1 - Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

AU - Ellinghaus, David

AU - Jostins, Luke

AU - Spain, Sarah L

AU - Cortes, Adrian

AU - Bethune, Jörn

AU - Han, Buhm

AU - Park, Yu Rang

AU - Raychaudhuri, Soumya

AU - Pouget, Jennie G

AU - Hübenthal, Matthias

AU - Folseraas, Trine

AU - Wang, Yunpeng

AU - Esko, Tonu

AU - Metspalu, Andres

AU - Westra, Harm-Jan

AU - Franke, Lude

AU - Pers, Tune H

AU - Weersma, Rinse K

AU - Collij, Valerie

AU - D'Amato, Mauro

AU - Halfvarson, Jonas

AU - Jensen, Anders Boeck

AU - Lieb, Wolfgang

AU - Degenhardt, Franziska

AU - Forstner, Andreas J

AU - Hofmann, Andrea

AU - Schreiber, Stefan

AU - Mrowietz, Ulrich

AU - Juran, Brian D

AU - Lazaridis, Konstantinos N

AU - Brunak, Søren

AU - Dale, Anders M

AU - Trembath, Richard C

AU - Weidinger, Stephan

AU - Weichenthal, Michael

AU - Ellinghaus, Eva

AU - Elder, James T

AU - Barker, Jonathan N W N

AU - Andreassen, Ole A

AU - McGovern, Dermot P

AU - Karlsen, Tom H

AU - Barrett, Jeffrey C

AU - Parkes, Miles

AU - Brown, Matthew A

AU - Franke, Andre

AU - International IBD Genetics Consortium (IIBDGC)

PY - 2016/5

Y1 - 2016/5

N2 - We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.

AB - We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European ancestry, we identified 244 independent multidisease signals, including 27 new genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multidisease signals with expression data sets from human, rat and mouse together with epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases genetically identical to those with another disease, possibly owing to diagnostic misclassification, molecular subtypes or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.

U2 - 10.1038/ng.3528

DO - 10.1038/ng.3528

M3 - Journal article

C2 - 26974007

VL - 48

SP - 510

EP - 521

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 5

ER -

ID: 159214100