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Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries.

Zhan Ju LiuRuize LiuHan GaoSeulgi JungXiang GaoRuicong SunXiaoming LiuYongjae KimHo-Su LeeYosuke KawaiMasao NagasakiJunji UmenoKatsushi TokunagaYoshitaka KinouchiAtsushi MasamuneWenzhao ShiChengguo ShenZhenglin GuoKai Yuannull nullnull nullnull nullShu ZhuDalin LiJian-Jun LiuTian GeJudy H ChoMark J DalyDermot P B McGovernByong Duk YeKyuyoung SongYoichi KakutaMing-Song LiHailiang Huang
Published in: Nature genetics (2023)
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 ~370,000 EUR individuals (~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.
Keyphrases
  • ulcerative colitis
  • genome wide
  • copy number
  • dna methylation
  • genome wide association study
  • gene expression
  • transcription factor