@article {Imboden1900457作者={美狄亚Imboden和马提亚Wielscher和费萨尔。Rezwan和{}\ ' e ~ F.S.Amaral和阿沙夫纳小桢和安娜Beckmeyer-Borowko莎拉·e·哈里斯和约翰•m•斯塔尔和伊恩~ J。亲爱的克劳迪娅弯曲和梅勒妮Waldenberger安妮特•彼得斯Holger舒尔茨和苏陈女孩儿汗阳光J.J. Karmaus右舵和Yu江Gertraud Erhart Florian Kronenberg和瑞安Arathimos吉玛·c·夏普和亚历山大·约翰·亨德森和傅昱和P{\“}新Piiril{\“}和Kirsi h . Pietil {\“} inen和Miina Ollikainen Asa约翰逊和Ulf Gyllensten Maaike de Vries和戴安娜a van der Plaat和金姆德容和h Marike Boezen和伊恩~ P。霍尔和马丁·d·托宾和Marjo-Riitta Jarvelin和约翰~ W。Holloway,黛博拉·贾维斯和妮可·m·Probst-Hensch} title = {Epigenome-wide协会研究肺功能水平及其变化},体积= {54}= {1},elocation-id = {1900457} = {2019}, doi ={10.1183/13993003.00457 -2019},出版商={欧洲呼吸学会},文摘={先前的报道链接微分DNA甲基化(DNAme)环境因素与肺功能相关。188bet官网地址然而,肺功能DNAme直接证据是有限的。我们进行了一个不可知论者epigenome-wide协会研究(ewa) pre-bronchodilation成人肺功能及其变化。在发现{\ textendash}复制ewa设计,DNAme在血液和肺量测定法测定两次,相隔6 {\ textendash} 15年,在相同的三个成年参与者以人群为基础的发现军团(n = 2043)。相关DNAme标记(p \ < 5 {\ texttimes} 10 - 7)测试结果在七复制军团(成人:n = 3327;童年:n = 420)。 Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96{\texttimes}10-21 and pcombined=7.22{\texttimes}10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65{\texttimes}10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.An agnostic association study on lung function using longitudinal population-based cohort data shows that differentially methylated genomic sites related to smoking are strongly associated with lung function in adults http://ow.ly/wYID30onUB4}, issn = {0903-1936}, URL = {//www.qdcxjkg.com/content/54/1/1900457}, eprint = {//www.qdcxjkg.com/content/54/1/1900457.full.pdf}, journal = {European Respiratory Journal} }