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We tested the hypothesis that<jats:italic>AHRR<\/jats:italic>hypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms in the general population.<\/jats:p><jats:p><jats:italic>AHRR<\/jats:italic>methylation extent was measured in 9113 individuals from the 1991\u20131994 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\u20132003.<\/jats:p><jats:p>Cross-sectionally, a 10% lower methylation extent was associated with a 0.2 z-score (95% CI 0.1\u20130.2) lower forced expiratory volume in 1\u2005s (FEV<jats:sub>1<\/jats:sub>) after multivariable adjustment including smoking. Hypomethylation was also associated with a lower z-score for both forced vital capacity (FVC) and FEV<jats:sub>1<\/jats:sub>\/FVC. In prospective analyses, individuals in the lowest<jats:italic>versus<\/jats:italic>highest tertile of methylation extent had a steeper decline in FEV<jats:sub>1<\/jats:sub>\/height<jats:sup>3<\/jats:sup>(p for examination\u00d7methylation interaction=0.003) and FVC\/height<jats:sup>3<\/jats:sup>(p=0.01), but not FEV<jats:sub>1<\/jats:sub>\/FVC (p=0.08). Multivariable-adjusted odds ratios per 10% lower methylation extent were 1.31 (95% CI 1.18\u20131.45) for chronic bronchitis and 1.21 (95% CI 1.13\u20131.30) for any respiratory symptoms.<\/jats:p><jats:p><jats:italic>AHRR<\/jats:italic>hypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.<\/jats:p>","DOI":"10.1183\/13993003.01512-2017","type":"journal-article","created":{"date-parts":[[2018,1,19]],"date-time":"2018-01-19T01:10:49Z","timestamp":1516324249000},"page":"1701512","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["<i>AHRR<\/i>hypomethylation, lung function, lung function decline and respiratory symptoms"],"prefix":"10.1183","volume":"51","author":[{"given":"Jakob B.","family":"Kodal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla 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