% 0期刊文章%美狄亚Imboden % Matthias Wielscher % Rezwan费萨尔i %安德烈F.S. Amaral % %阿沙夫纳一个小桢%一个莎拉·e·哈里斯安娜Beckmeyer-Borowko % %伊恩·J .亲爱的约翰·m·斯塔尔% %克劳迪娅弯曲%一个媚兰Waldenberger %安妮特•彼得斯% Holger舒尔茨%苏陈%一个女孩儿汗阳光% J.J. Karmaus %右一个玉江% Gertraud Erhart %一个瑞安Arathimos Florian Kronenberg % %吉玛c .急剧%亚历山大·约翰·亨德森%一个傅昱% Paivi Piirila % Kirsi h . Pietilainen % Miina Ollikainen %一个Ulf Gyllensten Asa约翰逊% % Maaike de Vries %一个戴安娜A . van der Plaat % Kim德容% h . Marike Boezen %伊恩·P·大厅%一个马丁·D·托宾% Marjo-Riitta Jarvelin %约翰·w·霍洛韦%黛博拉·贾维斯%妮可·m·Probst-Hensch % T Epigenome-wide协会研究肺功能水平及其变化% D 2019% R 10.1183/13993003.00457 -2019% J欧洲呼吸杂志% P 1900457 % V 54% N 1% X先前的报道链接微分DNA甲基化(DNAme)环境因素与肺功能相关。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discovery-replication ewa设计,DNAme在血液和肺量测定法测定两次,相隔6年,在同一参与者三个成年人群发现组(n = 2043)。相关DNAme标记(p < 5×10−7)在七个复制测试组(成人:n = 3327;童年:n = 420)。技术bias-adjusted剩余工资的回归正常化绝对β-values水平和变化控制probe-derived原理组件退化1 s的用力呼气量(FEV1)、用力肺活量(FVC)及其比率(FEV1 / FVC)在ewa covariate-adjusted发现。Inverse-variance-weighted荟萃分析结果进行发现和复制样本在所有参与者和不吸烟者。ewa信号是与吸烟有关的DNAme丰富。我们复制57 DNAme标记在成人肺功能,但不是童年样本,所有先前与吸烟有关。标记未与吸烟有关失败的复制。 cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10−21 and pcombined=7.22×10−50). 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=2.65×10−20).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 %U //www.qdcxjkg.com/content/erj/54/1/1900457.full.pdf