Data from: Epigenome-wide association study of lung function level and its change

Previous reports link differential DNA methylation (DNAme) to
environmental exposures which are associated with lung function. Direct
evidence on lung function DNAme is however limited. We undertook an
agnostic epigenome-wide association study (EWAS) on pre-bronchodilation
lung function and its change in adults. In a discovery-replication EWAS
design, DNAme in blood and spirometry were measured twice, six-to-15 years
apart, in the same participants of three adult population-based discovery
cohorts (n=2,043). Associated DNAme markers (P<5x10-7) were tested
in seven replication cohorts (adult: n=3,327; childhood: n=420).
Technical-bias adjusted residuals of a regression of the normalized
absolute beta-values on control-probe-derived principle components were
regressed on level and change of FEV1, FEV1/FVC and FVC in
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 in adult, but
not childhood samples, all previously associated with smoking. Markers not
previously associated with smoking failed replication. cg05575921 (AHRR)
showed the statistically most significant association with cross-sectional
lung function (FEV1/FVC: Pdiscovery=3.96x10-21 and Pcombined=7.22x10-50).
A score combining ten DNAme markers previously reported to mediate the
smoking effect on lung function was associated with lung function
(FEV1/FVC: P=2.65x10-20). 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.