小柯机器人

美国哈佛医学院Hailiang Huang等研究人员合作揭示了东亚和欧洲血统的炎症性肠病的遗传结构。相关论文于2023年5月8日发表在《自然—遗传学》杂志上。

研究人员表示，炎症性肠病（IBD）是胃肠道的慢性疾病，有以下两种亚型： 克罗恩病（CD）和溃疡性结肠炎（UC）。到目前为止，大多数IBD的遗传关联来自欧洲（EUR）血统的个体。研究人员报告了对东亚（EAS）血统个体的最大IBD研究，包括14393个病例和15456个对照。研究人员发现仅在EAS中就有80个IBD基因位点，在对约37万欧洲个体（约3万个病例）进行元分析时发现了320个，其中81个是新的。EAS富集的编码变体牵涉到许多新的IBD基因，包括ADAP1和GIT2。

虽然IBD的遗传效应在不同的祖先中一般是一致的，但CD的遗传学似乎比UC更依赖于祖先，由等位基因频率（NOD2）和效应（TNFSF15）驱动。研究人员扩展了IBD多基因风险评分（PRS），纳入了这两个祖先，大大提高了其准确性，并强调了多样性对PRS公平部署的重要性。

附：英文原文

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

Author: Liu, Zhanju, Liu, Ruize, Gao, Han, Jung, Seulgi, Gao, Xiang, Sun, Ruicong, Liu, Xiaoming, Kim, Yongjae, Lee, Ho-Su, Kawai, Yosuke, Nagasaki, Masao, Umeno, Junji, Tokunaga, Katsushi, Kinouchi, Yoshitaka, Masamune, Atsushi, Shi, Wenzhao, Shen, Chengguo, Guo, Zhenglin, Yuan, Kai, Zhu, Shu, Li, Dalin, Liu, Jianjun, Ge, Tian, Cho, Judy, Daly, Mark J., McGovern, Dermot P. B., Ye, Byong Duk, Song, Kyuyoung, Kakuta, Yoichi, Li, Mingsong, Huang, Hailiang

Issue&Volume: 2023-05-08

Abstract: 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.

DOI: 10.1038/s41588-023-01384-0

Source: https://www.nature.com/articles/s41588-023-01384-0

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex