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.

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.

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations / Liu, Jimmy Z; van Sommeren, Suzanne; Huang, Hailiang; Ng, Siew C; Alberts, Rudi; Takahashi, Atsushi; Ripke, Stephan; Lee, James C; Jostins, Luke; Shah, Tejas; Abedian, Shifteh; Cheon, Jae Hee; Cho, Judy; Daryani, Naser E; Franke, Lude; Fuyuno, Yuta; Hart, Ailsa; Juyal, Ramesh C; Juyal, Garima; Kim, Won Ho; Morris, Andrew P; Poustchi, Hossein; Newman, William G; Midha, Vandana; Orchard, Timothy R; Vahedi, Homayon; Sood, Ajit; Sung, Joseph J. Y; Malekzadeh, Reza; Westra, Harm Jan; Yamazaki, Keiko; Yang, Suk Kyun; Barrett, Jeffrey C; Franke, Andre; Alizadeh, Behrooz Z; Parkes, Miles; B. K, Thelma; Daly, Mark J; Kubo, Michiaki; Anderson, Carl A; Weersma, Rinse K; Abedian, S; Abraham, C; Achkar, Jp; Ahmad, T; Alberts, R; Alizadeh, B; Amininejad, L; Anathakrishnan, An; Andersen, V; Anderson, Ca; Andrews, Jm; Annese, V; Aumais, G; Baidoo, L; Baldassano, Rn; Balschun, T; Bampton, Pa; Barclay, M; Barrett, Jc; Bayless, Tm; Bethge, J; Bewshea, C; Bis, Jc; Bitton, A; B. K., T; Boucher, G; Brain, O; Brand, S; Brant, Sr; Büning, C; Cheon, Jh; Chew, A; Cho, Jh; Cleynen, I; Cohain, A; Cooney, R; Croft, A; Daly, Mj; D'Amato, M; Danese, S; Daryani, Ne; De Jong, D; de Lange, Km; De Vos, M; Denapiene, G; Denson, La; Devaney, Kl; Dewit, O; D'Inca, R; Drummond, He; Dubinsky, M; Duerr, Rh; Edwards, C; Ellinghaus, D; Esaki, M; Essers, J; Ferguson, Lr; Festen, Ea; Fleshner, P; Florin, T; Franchimont, D; Franke, A; Fransen, K; Fuyano, Y; Gearry, R; Georges, M; Gieger, C; Glas, J; Goyette, P; Green, T; Griffiths, Am; Guthery, Sl; Hakonarson, H; Halfvarson, J; Hanigan, K; Haritunians, T; Hart, A; Hawkey, C; Hayward, Nk; Hedl, M; Henderson, P; Hold, Gl; Hu, X; Huang, H; Hui, Ky; Imielinski, M; Ippoliti, A; Jazayeri, O; Jonaitis, L; Jostins, L; Juyal, G; Juyal, Rc; Kalla, R; Karlsen, Th; Kawaguchi, T; Kennedy, Na; Khan, Ma; Kim, Wh; Kitazono, T; Kiudelis, G; Kubo, M; Kugathasan, S; Kupcinskas, L; Lamb, Ca; Latiano, A; Laukens, D; Lawrance, Ic; Lee, Jc; Lees, Cw; Leja, M; Lewis, N; Van Limbergen, J; Lionetti, P; Liu, Jz; Louis, E; Luo, Y; Mahy, G; Malekzadeh, Mm; Malekzadeh, R; Mansfield, J; Marriott, S; Massey, D; Mathew, Cg; Matsui, T; McGovern, Dp; Midha, V; Milgrom, R; Mirzaei, S; Mitrovic, M; Montgomery, Gw; Motoya, S; Mowat, C; Newman, Wg; Ng, A; Ng, Sc; Ng, Sm; Nikolaus, S; Nimmo, Er; Ning, K; Nöthen, M; Oikonomou, I; Orchard, Tr; Palmieri, O; Parkes, M; Phillips, A; Ponsioen, Cy; Potocnik, U; Poustchi, H; Prescott, Nj; Proctor, Dd; Radford Smith, G; Rahier, Jf; Raychaudhuri, S; Regueiro, M; Rieder, F; Rioux, Jd; Ripke, S; Roberts, R; Russell, Rk; Sanderson, Jd; Sans, M; Satsangi, J; Schadt, Ee; Schreiber, S; Schumm, Lp; Scott, R; Seielstad, M; Shah, T; Sharma, Y; Silverberg, Ms; Simmons, A; Simms, La; Singh, A; Skieceviciene, J; Sood, A; Spain, Sl; Steinhart, Ah; Stempak, Jm; Stronati, Laura; Sung, Jj; Suzuki, Y; Sventoraityte, J; Takahashi, A; Takazoe, M; Tanaka, H; Taylor, Km; ter Velde, A; Theatre, E; Torkvist, L; Tremelling, M; Uhlig, Hh; Vahedi, H; van der Meulen, A; van Sommeren, S; Vasiliauskas, E; Ventham, Nt; Vermeire, S; Verspaget, Hw; Walters, T; Wang, K; Wang, Mh; Weersma, Rk; Wei, Z; Whiteman, D; Wijmenga, C; Wilson, Dc; Winkelmann, J; Xavier, Rj; Yamada, T; Yamazaki, K; Zeissig, S; Zhang, B; Zhang, Ck; Zhang, H; Zhang, W; Zhao, H; Zhao, Zz. - In: NATURE GENETICS. - ISSN 1546-1718. - STAMPA. - 47:9(2015), p. 979-86.

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

STRONATI, LAURA;
2015

Abstract

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.
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.
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