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Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries
Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China; .ORCID iD: 0000-0002-0326-543X
Örebro University, School of Medical Sciences. Department of Gastroenterology.ORCID iD: 0000-0003-0122-7234
Department of Gastroenterology, Suzhou Hospital of Anhui Medical University, Suzhou, China.
Number of Authors: 1082023 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 55, no 5, p. 796-806Article in journal (Refereed) Published
Abstract [en]

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract with the following two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). To date, most IBD genetic associations were derived from individuals of European (EUR) ancestries. Here we report the largest IBD study of individuals of East Asian (EAS) ancestries, including 14,393 cases and 15,456 controls. We found 80 IBD loci in EAS alone and 320 when meta-analyzed with similar to 370,000 EUR individuals (similar to 30,000 cases), among which 81 are new. EAS-enriched coding variants implicate many new IBD genes, including ADAP1 and GIT2. Although IBD genetic effects are generally consistent across ancestries, genetics underlying CD appears more ancestry dependent than UC, driven by allele frequency (NOD2) and effect (TNFSF15). We extended the IBD polygenic risk score (PRS) by incorporating both ancestries, greatly improving its accuracy and highlighting the importance of diversity for the equitable deployment of PRS. Genome-wide association analyses across individuals of East Asian and European ancestries identify new risk loci for inflammatory bowel diseases. A polygenic risk score derived from the combined datasets shows improved prediction accuracy.

Place, publisher, year, edition, pages
Nature Portfolio , 2023. Vol. 55, no 5, p. 796-806
National Category
Medical Genetics and Genomics
Identifiers
URN: urn:nbn:se:oru:diva-107329DOI: 10.1038/s41588-023-01384-0ISI: 000992489700001PubMedID: 37156999Scopus ID: 2-s2.0-85158880855OAI: oai:DiVA.org:oru-107329DiVA, id: diva2:1785312
Funder
AstraZenecaPfizer ABAvailable from: 2023-08-02 Created: 2023-08-02 Last updated: 2025-02-10Bibliographically approved

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Halfvarson, Jonas

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