Replication and meta-analyses
Genome-wide significant CpG sites that passed Bonferroni correction
(P< 1.14×10-7, which is 0.05 / 436,824) in
whole blood DNA were selected for replication in two independent
cohorts, Lifelines and EGEA. Lifelines did not include an assessment of
AHR, so only included a ClinR phenotype available for replication. The
weighted Z-score method was used to meta-analyze the results of
discovery and replication cohorts, considering EGEA used methylC-capture
sequencing method, which was different from discovery and Lifelines
(450K array), to investigate DNA methylation. CpG sites that passed the
epigenome-wide significance threshold of P<
1.14×10-7 (Bonferroni correction) in the meta-analysis
of all studies were considered to be replicated. Finally, top sites
identified in whole blood were verified in nasal brushes.