RT Journal Article SR Electronic T1 AHRR hypomethylation, lung function, lung function decline and respiratory symptoms JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1701512 DO 10.1183/13993003.01512-2017 VO 51 IS 3 A1 Jakob B. Kodal A1 Camilla J. Kobylecki A1 Signe Vedel-Krogh A1 Børge G. Nordestgaard A1 Stig E. Bojesen YR 2018 UL http://erj.ersjournals.com/content/51/3/1701512.abstract AB Epigenome-wide association studies have shown a consistent association between smoking exposure and hypomethylation in the aryl hydrocarbon receptor repressor (AHRR) gene (cg05575921). We tested the hypothesis that AHRR hypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms in the general population.AHRR methylation extent was measured in 9113 individuals from the 1991–1994 examination of the Copenhagen City Heart Study, using bisulfite-treated leukocyte DNA. Spirometry at the time of blood sampling was available for all individuals. Lung function was measured again for 4532 of these individuals in 2001–2003.Cross-sectionally, a 10% lower methylation extent was associated with a 0.2 z-score (95% CI 0.1–0.2) lower forced expiratory volume in 1 s (FEV1) after multivariable adjustment including smoking. Hypomethylation was also associated with a lower z-score for both forced vital capacity (FVC) and FEV1/FVC. In prospective analyses, individuals in the lowest versus highest tertile of methylation extent had a steeper decline in FEV1/height3 (p for examination×methylation interaction=0.003) and FVC/height3 (p=0.01), but not FEV1/FVC (p=0.08). Multivariable-adjusted odds ratios per 10% lower methylation extent were 1.31 (95% CI 1.18–1.45) for chronic bronchitis and 1.21 (95% CI 1.13–1.30) for any respiratory symptoms.AHRR hypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.AHRR hypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms http://ow.ly/a30J30hB2dS