全基因组荟萃分析将确认的克罗恩病易感性位点数量增加到 71 个。
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
机构信息
Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany.
出版信息
Nat Genet. 2010 Dec;42(12):1118-25. doi: 10.1038/ng.717.
Abstract
We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
摘要
我们对六项克罗恩病全基因组关联研究（GWAS）进行了荟萃分析，共纳入 6333 名受影响个体（病例）和 15056 名对照，并对 15694 例病例、14026 名对照和 414 对父母-子女三胞胎中的最高关联信号进行了随访。我们确定了 30 个新的易感性位点，达到全基因组显著水平（P < 5 × 10⁻⁸）。一系列的计算分析突出了这些位点内的特定基因，并与人工整理一起，暗示了具有功能意义的候选基因，包括 SMAD3、ERAP2、IL10、IL2RA、TYK2、FUT2、DNMT3A、DENND1B、BACH2 和 TAGAP。结合以前确认的位点，这些结果确定了 71 个不同的位点，这些位点与克罗恩病的全基因组显著关联具有全基因组显著证据。
相似文献
1
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.全基因组荟萃分析将确认的克罗恩病易感性位点数量增加到 71 个。
Nat Genet. 2010 Dec;42(12):1118-25. doi: 10.1038/ng.717.
2
A genome-wide association study identifies 2 susceptibility Loci for Crohn's disease in a Japanese population.全基因组关联研究在日本人群中发现克罗恩病的 2 个易感基因座。
Gastroenterology. 2013 Apr;144(4):781-8. doi: 10.1053/j.gastro.2012.12.021. Epub 2012 Dec 22.
3
A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn's disease and celiac disease.一项全基因组关联扫描的荟萃分析确定 IL18RAP、PTPN2、TAGAP 和 PUS10 为克罗恩病和乳糜泻的共同风险基因座。
PLoS Genet. 2011 Jan 27;7(1):e1001283. doi: 10.1371/journal.pgen.1001283.
4
Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci.对克罗恩病和银屑病的全基因组关联研究进行联合分析，确定了七个共同的易感性位点。
Am J Hum Genet. 2012 Apr 6;90(4):636-47. doi: 10.1016/j.ajhg.2012.02.020.
5
Susceptibility loci reported in genome-wide association studies are associated with Crohn's disease in Canadian children.全基因组关联研究中报道的易感性基因座与加拿大儿童的克罗恩病有关。
Aliment Pharmacol Ther. 2010 Jun;31(11):1186-91. doi: 10.1111/j.1365-2036.2010.04294.x. Epub 2010 Mar 8.
6
Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations.韩国人克罗恩病的全基因组关联研究揭示了三个新的易感基因座，以及不同种族人群遗传易感性的共同特征。
Gut. 2014 Jan;63(1):80-7. doi: 10.1136/gutjnl-2013-305193. Epub 2013 Jul 14.
7
A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus at RBX1-EP300.在一个南欧人群中进行的全基因组关联研究鉴定出 RBX1-EP300 处克罗恩病易感性新位点。
Gut. 2013 Oct;62(10):1440-5. doi: 10.1136/gutjnl-2012-302865. Epub 2012 Aug 30.
8
Immunochip analysis identification of 6 additional susceptibility loci for Crohn's disease in Koreans.免疫芯片分析在韩国人中鉴定出另外6个克罗恩病易感基因座。
Inflamm Bowel Dis. 2015 Jan;21(1):1-7. doi: 10.1097/MIB.0000000000000268.
9
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease.全基因组关联研究确定了30多个克罗恩病的不同易感基因座。
Nat Genet. 2008 Aug;40(8):955-62. doi: 10.1038/ng.175. Epub 2008 Jun 29.
10
Genome-wide association studies and Crohn's disease.全基因组关联研究与克罗恩病。
Brief Funct Genomics. 2011 Mar;10(2):71-6. doi: 10.1093/bfgp/elr009.
引用本文的文献
1
Autophagy and Bacterial infections.自噬与细菌感染
Autophagy Rep. 2025 Sep 1;4(1):2542904. doi: 10.1080/27694127.2025.2542904. eCollection 2025.
2
Heterozygous variants in affect hearing, vision, cardiac, and immune function.[基因名称]中的杂合变异会影响听力、视力、心脏和免疫功能。 （注：原文中“in”后面缺少具体基因名称，需补充完整才能准确翻译）
Elife. 2025 Aug 27;13:RP95887. doi: 10.7554/eLife.95887.
3
Identifying the genetic basis and molecular mechanisms underlying phenotypic correlation between complex human traits using a gene-based approach.使用基于基因的方法来确定复杂人类性状之间表型相关性背后的遗传基础和分子机制。
bioRxiv. 2025 Jul 27:2021.02.09.430368. doi: 10.1101/2021.02.09.430368.
4
Guardians of silence: transcriptional networks in T cell quiescence.沉默守护者：T细胞静止状态下的转录网络
Exp Mol Med. 2025 Aug 4. doi: 10.1038/s12276-025-01516-y.
5
BACH2 drives the development and function of group 2 innate lymphoid cells.BACH2驱动2型固有淋巴细胞的发育和功能。
Sci Adv. 2025 Aug;11(31):eads4323. doi: 10.1126/sciadv.ads4323. Epub 2025 Aug 1.
6
Role of adiponectin and its receptors AdipoR1/2 in inflammatory bowel disease.脂联素及其受体AdipoR1/2在炎症性肠病中的作用
Cell Commun Signal. 2025 Jul 26;23(1):356. doi: 10.1186/s12964-025-02359-w.
7
Current progress and future perspective of super-enhancers: a viable and effective bridge between the transcriptional apparatus and disease.超级增强子的当前进展与未来展望：转录装置与疾病之间可行且有效的桥梁
Front Genet. 2025 Jul 2;16:1611905. doi: 10.3389/fgene.2025.1611905. eCollection 2025.
8
ATF7IP/SETDB1-mediated epigenetic programming regulates thymic homing and T lymphopoiesis of hematopoietic progenitors during embryogenesis.ATF7IP/SETDB1介导的表观遗传编程在胚胎发育过程中调节造血祖细胞的胸腺归巢和T淋巴细胞生成。
Nat Commun. 2025 Jul 16;16(1):6550. doi: 10.1038/s41467-025-61680-7.
9
Combined approaches to reduce stress and improve livestock well-being: A review.减轻压力并改善家畜健康的综合方法：综述
Cell Stress Chaperones. 2025 Jul 9;30(5):100091. doi: 10.1016/j.cstres.2025.100091.
10
The cAMP responsive element modulator (CREM) transcription factor influences susceptibility to undernutrition and infection.环磷酸腺苷反应元件调节因子（CREM）转录因子会影响对营养不良和感染的易感性。
mBio. 2025 Jun 27:e0139025. doi: 10.1128/mbio.01390-25.
本文引用的文献
1
Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease.岩藻糖基转移酶 2（FUT2）非分泌状态与克罗恩病有关。
Hum Mol Genet. 2010 Sep 1;19(17):3468-76. doi: 10.1093/hmg/ddq248. Epub 2010 Jun 22.
2
Common SNPs explain a large proportion of the heritability for human height.常见的单核苷酸多态性解释了人类身高遗传的很大一部分。
Nat Genet. 2010 Jul;42(7):565-9. doi: 10.1038/ng.608. Epub 2010 Jun 20.
3
Estimation of effect size distribution from genome-wide association studies and implications for future discoveries.从全基因组关联研究中估计效应大小分布及其对未来发现的影响。
Nat Genet. 2010 Jul;42(7):570-5. doi: 10.1038/ng.610. Epub 2010 Jun 20.
4
Role of SMAD and non-SMAD signals in the development of Th17 and regulatory T cells.SMAD 和非 SMAD 信号在 Th17 和调节性 T 细胞发育中的作用。
J Immunol. 2010 Apr 15;184(8):4295-306. doi: 10.4049/jimmunol.0903418. Epub 2010 Mar 19.
5
Variants of DENND1B associated with asthma in children.与儿童哮喘相关的 DENND1B 变异体。
N Engl J Med. 2010 Jan 7;362(1):36-44. doi: 10.1056/NEJMoa0901867. Epub 2009 Dec 23.
6
Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study.在一项针对17686名女性的纤维蛋白原全基因组关联研究中发现的新基因座，包括与克罗恩病、银屑病和炎症相关的基因座：女性基因组健康研究。
Circ Cardiovasc Genet. 2009 Apr;2(2):134-41. doi: 10.1161/CIRCGENETICS.108.825273. Epub 2009 Feb 12.
7
Common variants at five new loci associated with early-onset inflammatory bowel disease.五个新的与早发性炎症性肠病相关的常见变异位点。
Nat Genet. 2009 Dec;41(12):1335-40. doi: 10.1038/ng.489. Epub 2009 Nov 15.
8
Inflammatory bowel disease and mutations affecting the interleukin-10 receptor.炎症性肠病与影响白细胞介素-10受体的突变
N Engl J Med. 2009 Nov 19;361(21):2033-45. doi: 10.1056/NEJMoa0907206. Epub 2009 Nov 4.
9
Phenopedia and Genopedia: disease-centered and gene-centered views of the evolving knowledge of human genetic associations.表型组学与基因组学：从疾病和基因角度看待人类遗传关联知识的演进
Bioinformatics. 2010 Jan 1;26(1):145-6. doi: 10.1093/bioinformatics/btp618. Epub 2009 Oct 27.
10
Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource.利用基因型可选择的人类生物资源对自身免疫基因座IL2RA进行细胞特异性蛋白质表型分析。
Nat Genet. 2009 Sep;41(9):1011-5. doi: 10.1038/ng.434. Epub 2009 Aug 23.
Zotero 插件