Therapeutic targets for inflammatory bowel disease: proteome-wide Mendelian randomization and colocalization analyses

孟德尔随机化 炎症性肠病 共域化 蛋白质组 PTPN22型 全基因组关联研究 医学 疾病 生物信息学 单核苷酸多态性 生物 免疫学 遗传学 内科学 基因 遗传变异 分子生物学 基因型
作者
Jie Chen,Fengzhe Xu,Xixian Ruan,Jing Sun,Yao Zhang,Han Zhang,Jianhui Zhao,Jie Zheng,Susanna C. Larsson,Xiaoyan Wang,Xue Li,Shuai Yuan
出处
期刊:EBioMedicine [Elsevier BV]
卷期号:89: 104494-104494 被引量:113
标识
DOI:10.1016/j.ebiom.2023.104494
摘要

Identifying new drug targets for inflammatory bowel disease (IBD) is urgently needed. The proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) and colocalization analyses to identify possible targets for IBD.Summary-level data of 4907 circulating protein levels were extracted from a large-scale protein quantitative trait loci study including 35,559 individuals. Genetic associations with IBD and its subtypes were obtained from the Inflammatory Bowel Disease Genetics Consortium (25,024 cases and 34,915 controls), the FinnGen study (7206 cases and 253,199 controls), and the UK Biobank study (7045 cases and 449,282 controls). MR analysis was conducted to estimate the associations between protein and IBD risk. The colocalization analysis was used to examine whether the identified proteins and IBD shared casual variants.Genetically predicted levels of 3, and 5 circulating proteins were associated with IBD and ulcerative colitis (UC), respectively. With high supporting evidence of colocalization, genetically predicted MST1 (macrophage stimulating 1) and HGFAC (hepatocyte growth factor activator) levels were inversely associated with IBD risks. The associations of STAT3 (signal transducer and activator of transcription 3), MST1, CXCL5 (C-X-C motif chemokine ligand 5), and ITPKA (inositol-trisphosphate 3-kinase A) with the risk of UC were supported by colocalization analysis.The proteome-wide MR investigation identified many proteins associated with the risk of IBD. MST1, HGFAC, STAT3, ITPKA, and CXCL5 deserve further investigation as potential therapeutic targets for IBD.SCL is supported by research grants from the Swedish Research Council for Health, Working Life and Welfare (Forte; grant no. 2018-00123) and the Swedish Research Council (Vetenskapsrådet; grant no. 2019-00977). XYW is supported by research grants from the National Natural Science Foundation of China (81970494) and Key Project of Research and Development Plan of Hunan Province (2019SK2041). XL is supported by research grants from the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001).
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
安安完成签到,获得积分10
刚刚
啊啊啊啊完成签到,获得积分10
刚刚
英俊的铭应助飞飞鱼采纳,获得10
2秒前
科目三应助zzz采纳,获得10
2秒前
小小西瓜萝卜青菜完成签到,获得积分10
2秒前
思源应助虚幻采枫采纳,获得10
3秒前
3秒前
不安的可乐完成签到,获得积分10
3秒前
4秒前
nano完成签到 ,获得积分10
4秒前
da完成签到,获得积分10
4秒前
科研通AI2S应助啊啊啊啊采纳,获得10
5秒前
cyndi发布了新的文献求助20
5秒前
6秒前
852应助小小西瓜萝卜青菜采纳,获得10
8秒前
sci完成签到,获得积分10
9秒前
醉熏的鑫发布了新的文献求助10
10秒前
Nizarn发布了新的文献求助10
10秒前
11秒前
11秒前
乐呵呵完成签到,获得积分10
11秒前
11秒前
忧心的惜天完成签到 ,获得积分10
11秒前
77完成签到,获得积分10
12秒前
yz发布了新的文献求助10
12秒前
周周南完成签到 ,获得积分10
15秒前
15秒前
zz完成签到,获得积分10
15秒前
自由老头应助cyndi采纳,获得20
16秒前
努力做实验完成签到 ,获得积分10
17秒前
wf发布了新的文献求助10
17秒前
研友_ngkEgn完成签到,获得积分10
17秒前
代丽娟完成签到,获得积分10
17秒前
19秒前
快来下载文献完成签到,获得积分10
19秒前
苹果山芙完成签到,获得积分10
20秒前
煎饼狗子发布了新的文献求助10
20秒前
r41r32完成签到 ,获得积分10
21秒前
22秒前
QQ完成签到,获得积分10
23秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds第二卷 1200
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038657
求助须知:如何正确求助?哪些是违规求助? 3576306
关于积分的说明 11375198
捐赠科研通 3306108
什么是DOI,文献DOI怎么找? 1819379
邀请新用户注册赠送积分活动 892698
科研通“疑难数据库(出版商)”最低求助积分说明 815066