title: Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.
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.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Jimmy Z
authors.initials: JZ
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.|Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Sommeren
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong.
authors.forename: Siew C
authors.initials: SC
authors.lastname: Ng
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rudi
authors.initials: R
authors.lastname: Alberts
authors.affiliation: Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.affiliation: Inflammatory Bowel Disease Research Group, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: James C
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Jostins
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Tejas
authors.initials: T
authors.lastname: Shah
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran, Iran.
authors.forename: Shifteh
authors.initials: S
authors.lastname: Abedian
authors.affiliation: Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
authors.affiliation: Icahn School of Medicine, Mount Sinai New York, New York, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Gastroenterology, Emam Hospital, Tehran, Iran.
authors.forename: Naser E
authors.initials: NE
authors.lastname: Dayani
authors.affiliation: Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.affiliation: Laboratory for Genotyping Development, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Fuyuno
authors.affiliation: IBD Unit, St Mark's Hospital, Harrow, Middlesex, UK.
authors.forename: Ailsa
authors.initials: A
authors.lastname: Hart
authors.affiliation: National Institute of Immunology, Aruna Asaf Ali Road, New Delhi, India.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Juyal
authors.affiliation: Department of Genetics, University of Delhi South Campus, New Delhi, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Juyal
authors.affiliation: Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Welcome Trust Center for Human Genetics, Oxford U.K. and Department of Biostatistics, University of Liverpool, Liverpool, UK.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Poustchi
authors.affiliation: Manchester Centre for Genomic Medicine, University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: William G
authors.initials: WG
authors.lastname: Newman
authors.affiliation: Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India.
authors.forename: Vandana
authors.initials: V
authors.lastname: Midha
authors.affiliation: St Mary's Hospital, London, UK.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Orchard
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran, Iran.
authors.forename: Homayon
authors.initials: H
authors.lastname: Vahedi
authors.affiliation: Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India.
authors.forename: Ajit
authors.initials: A
authors.lastname: Sood
authors.affiliation: Department of Medicine and Therapeutics, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong.
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Sung
authors.affiliation: Digestive Disease Research Institute, Shariati Hospital, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.affiliation: Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Harm-Jan
authors.initials: HJ
authors.lastname: Westra
authors.affiliation: Laboratory for Genotyping Development, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Asan Medical Center, University of Ulsan College Medicine, Seoul, Korea.
authors.forename: Suk-Kyun
authors.initials: SK
authors.lastname: Yang
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Barrett
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Behrooz Z
authors.initials: BZ
authors.lastname: Alizadeh
authors.affiliation: Inflammatory Bowel Disease Research Group, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Miles
authors.initials: M
authors.lastname: Parkes
authors.affiliation: Department of Genetics, University of Delhi South Campus, New Delhi, India.
authors.forename: Thelma
authors.initials: T
authors.lastname: Bk
authors.affiliation: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.affiliation: Laboratory for Genotyping Development, Center for Integrative Medical Sciences, Riken, Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Anderson
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rinse K
authors.initials: RK
authors.lastname: Weersma
mesh_terms: D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors