Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis

Author:

Olafsdottir Thorunn A.,Theodors Fannar,Bjarnadottir Kristbjorg,Bjornsdottir Unnur Steina,Agustsdottir Arna B.,Stefansson Olafur A.,Ivarsdottir Erna V.ORCID,Sigurdsson Jon K.,Benonisdottir Stefania,Eyjolfsson Gudmundur I.,Gislason David,Gislason Thorarinn,Guðmundsdóttir Steinunn,Gylfason Arnaldur,Halldorsson Bjarni V.ORCID,Halldorsson Gisli H.ORCID,Juliusdottir Thorhildur,Kristinsdottir Anna M.,Ludviksdottir Dora,Ludviksson Bjorn R.,Masson Gisli,Norland Kristjan,Onundarson Pall T.,Olafsson Isleifur,Sigurdardottir Olof,Stefansdottir Lilja,Sveinbjornsson Gardar,Tragante ViniciusORCID,Gudbjartsson Daniel F.ORCID,Thorleifsson Gudmar,Sulem PatrickORCID,Thorsteinsdottir Unnur,Norddahl Gudmundur L.,Jonsdottir IngileifORCID,Stefansson KariORCID

Abstract

AbstractAsthma is one of the most common chronic diseases affecting both children and adults. We report a genome-wide association meta-analysis of 69,189 cases and 702,199 controls from Iceland and UK biobank. We find 88 asthma risk variants at 56 loci, 19 previously unreported, and evaluate their effect on other asthma and allergic phenotypes. Of special interest are two low frequency variants associated with protection against asthma; a missense variant in TNFRSF8 and 3‘ UTR variant in TGFBR1. Functional studies show that the TNFRSF8 variant reduces TNFRSF8 expression both on cell surface and in soluble form, acting as loss of function. eQTL analysis suggests that the TGFBR1 variant acts through gain of function and together with an intronic variant in a downstream gene, SMAD3, points to defective TGFβR1 signaling as one of the biological perturbations increasing asthma risk. Our results increase the number of asthma variants and implicate genes with known role in T cell regulation, inflammation and airway remodeling in asthma pathogenesis.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

Cited by 65 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3