Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

J.Z. Z. Liu; S. Van Sommeren; H. Huang; S.C. C. Ng; R. Alberts; A. Takahashi; S. Ripke; J.C. C. Lee; L. Jostins; T. Shah; S. Abedian; J.H. H. Cheon; J. Cho; N.E. E. Daryani; L. Franke; Y. Fuyuno; A. Hart; R.C. C. Juyal; G. Juyal; W.H. H. Kim; A.P. P. Morris; H. Poustchi; W.G. G. Newman; V. Midha; T.R. R. Orchard; H. Vahedi; A. Sood; J.J.Y. J.Y. Sung; R. Malekzadeh; H.J. J. Westra; K. Yamazaki; S.K. K. Yang; J.C. C. Barrett; A. Franke; B.Z. Z. Alizadeh; M. Parkes; B.K. K. Thelma; M.J. J. Daly; M. Kubo; C.A. A. Anderson; R.K. K. Weersma; Angela Baird; Ian Lawrance

doi:10.1038/ng.3359

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

J.Z. Z. Liu, S. Van Sommeren, H. Huang, S.C. C. Ng, R. Alberts, A. Takahashi, S. Ripke, J.C. C. Lee, L. Jostins, T. Shah, S. Abedian, J.H. H. Cheon, J. Cho, N.E. E. Daryani, L. Franke, Y. Fuyuno, A. Hart, R.C. C. Juyal, G. Juyal, W.H. H. KimA.P. P. Morris, H. Poustchi, W.G. G. Newman, V. Midha, T.R. R. Orchard, H. Vahedi, A. Sood, J.J.Y. J.Y. Sung, R. Malekzadeh, H.J. J. Westra, K. Yamazaki, S.K. K. Yang, J.C. C. Barrett, A. Franke, B.Z. Z. Alizadeh, M. Parkes, B.K. K. Thelma, M.J. J. Daly, M. Kubo, C.A. A. Anderson, R.K. K. Weersma, Angela Baird, Ian Lawrance

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Abstract

© 2015 Nature America, Inc. All rights reserved.Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.

Original language	English
Pages (from-to)	979-986
Number of pages	8
Journal	Nature Genetics
Volume	47
Issue number	9
DOIs	https://doi.org/10.1038/ng.3359
Publication status	Published - 2015

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Liu, J. Z. Z., Van Sommeren, S., Huang, H., Ng, S. C. C., Alberts, R., Takahashi, A., Ripke, S., Lee, J. C. C., Jostins, L., Shah, T., Abedian, S., Cheon, J. H. H., Cho, J., Daryani, N. E. E., Franke, L., Fuyuno, Y., Hart, A., Juyal, R. C. C., Juyal, G., ... Lawrance, I. (2015). Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nature Genetics, 47(9), 979-986. https://doi.org/10.1038/ng.3359

@article{b3d57145957745aab414319081179370,

title = "Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations",

abstract = "{\textcopyright} 2015 Nature America, Inc. All rights reserved.Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.",

author = "Liu, {J.Z. Z.} and {Van Sommeren}, S. and H. Huang and Ng, {S.C. C.} and R. Alberts and A. Takahashi and S. Ripke and Lee, {J.C. C.} and L. Jostins and T. Shah and S. Abedian and Cheon, {J.H. H.} and J. Cho and Daryani, {N.E. E.} and L. Franke and Y. Fuyuno and A. Hart and Juyal, {R.C. C.} and G. Juyal and Kim, {W.H. H.} and Morris, {A.P. P.} and H. Poustchi and Newman, {W.G. G.} and V. Midha and Orchard, {T.R. R.} and H. Vahedi and A. Sood and Sung, {J.J.Y. J.Y.} and R. Malekzadeh and Westra, {H.J. J.} and K. Yamazaki and Yang, {S.K. K.} and Barrett, {J.C. C.} and A. Franke and Alizadeh, {B.Z. Z.} and M. Parkes and Thelma, {B.K. K.} and Daly, {M.J. J.} and M. Kubo and Anderson, {C.A. A.} and Weersma, {R.K. K.} and Angela Baird and Ian Lawrance",

year = "2015",

doi = "10.1038/ng.3359",

language = "English",

volume = "47",

pages = "979--986",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group - Macmillan Publishers",

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}

Liu, JZZ, Van Sommeren, S, Huang, H, Ng, SCC, Alberts, R, Takahashi, A, Ripke, S, Lee, JCC, Jostins, L, Shah, T, Abedian, S, Cheon, JHH, Cho, J, Daryani, NEE, Franke, L, Fuyuno, Y, Hart, A, Juyal, RCC, Juyal, G, Kim, WHH, Morris, APP, Poustchi, H, Newman, WGG, Midha, V, Orchard, TRR, Vahedi, H, Sood, A, Sung, JJYJY, Malekzadeh, R, Westra, HJJ, Yamazaki, K, Yang, SKK, Barrett, JCC, Franke, A, Alizadeh, BZZ, Parkes, M, Thelma, BKK, Daly, MJJ, Kubo, M, Anderson, CAA, Weersma, RKK, Baird, A & Lawrance, I 2015, 'Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations', Nature Genetics, vol. 47, no. 9, pp. 979-986. https://doi.org/10.1038/ng.3359

TY - JOUR

T1 - Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

AU - Liu, J.Z. Z.

AU - Van Sommeren, S.

AU - Huang, H.

AU - Ng, S.C. C.

AU - Alberts, R.

AU - Takahashi, A.

AU - Ripke, S.

AU - Lee, J.C. C.

AU - Jostins, L.

AU - Shah, T.

AU - Abedian, S.

AU - Cheon, J.H. H.

AU - Cho, J.

AU - Daryani, N.E. E.

AU - Franke, L.

AU - Fuyuno, Y.

AU - Hart, A.

AU - Juyal, R.C. C.

AU - Juyal, G.

AU - Kim, W.H. H.

AU - Morris, A.P. P.

AU - Poustchi, H.

AU - Newman, W.G. G.

AU - Midha, V.

AU - Orchard, T.R. R.

AU - Vahedi, H.

AU - Sood, A.

AU - Sung, J.J.Y. J.Y.

AU - Malekzadeh, R.

AU - Westra, H.J. J.

AU - Yamazaki, K.

AU - Yang, S.K. K.

AU - Barrett, J.C. C.

AU - Franke, A.

AU - Alizadeh, B.Z. Z.

AU - Parkes, M.

AU - Thelma, B.K. K.

AU - Daly, M.J. J.

AU - Kubo, M.

AU - Anderson, C.A. A.

AU - Weersma, R.K. K.

AU - Baird, Angela

AU - Lawrance, Ian

PY - 2015

Y1 - 2015

N2 - © 2015 Nature America, Inc. All rights reserved.Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.

AB - © 2015 Nature America, Inc. All rights reserved.Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.

U2 - 10.1038/ng.3359

DO - 10.1038/ng.3359

M3 - Article

SN - 1061-4036

VL - 47

SP - 979

EP - 986

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

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