CpG | Chr. | Position (hg19) | Locus | Combined meta-analysis (ECRHS/NFBC1966/SAPALDIA/KORA/LBC1936/Lifelines/NSPHS) | Previously reported smoking CpGƒ | Previously reported smoking pFDR-valueƒ | Previously reported smoking association direction of effectƒ | ||||
β#±se | p-value meta-analysis | Direction of effects+ | p-value between-study heterogeneity | Replicated p<0.0011§ | |||||||
cg09884077 | 15 | 23 086 698 | NIPA1 | −0.308±0.084 | 0.0003 | −/−/−/+/−/−/− | 0.001 | No | No | NA | NA |
cg25758394 | 1 | 3 623 859 | TP73 | 0.213±0.083 | 0.0107 | ?/?/+/−/−/+/− | <0.001 | No | No | NA | NA |
cg18664508 | 3 | 169 487 465 | ARPM1 | −0.308±0.072 | 2.02×10−5 | +/−/−/−/−/−/− | <0.001 | No | No | NA | NA |
cg19268386 | 15 | 23 086 595 | NIPA1 | −0.263±0.140 | 0.0615 | ?/?/−/−/−/−/− | <0.001 | No | No | NA | NA |
cg15981995 | 3 | 169 487 311 | ARPM1 | −0.231±0.073 | 0.0016 | ?/?/−/−/−/−/+ | <0.001 | No | No | NA | NA |
cg05785298 | 1 | 204 654 622 | LRRN2 | −0.423±0.111 | 1.41×10−4 | −/+/−/+/−/+/− | 0.001 | No | No | NA | NA |
cg20278790 | 20 | 57 583 474 | CTSZ | 0.319±0.070 | 5.01×10−6 | −/+/+/+/−/−/− | <0.001 | No | No | NA | NA |
cg13562246 | 8 | 33 368 277 | C8orf41 | 0.349±0.074 | 2.67×10−6 | +/+/+/+/+/−/+ | 0.206 | No | No | NA | NA |
Chr.: chromosome; hg19: human genome build 19; β: coefficient of association; FDR: false discovery rate; NA: not assessed. For complete results for FEV1/FVC and for FEV1 and FVC in never-smokers, see supplementary table S8. #: presentation of CpG markers showing meta-analysis p<5×10−7 at discovery level for cross-sectional association at time-point 2, using data from time-point 2 of ECRHS, NFBC1966, SAPALDIA and LBC1936 and from time-point 1 of KORA, LifeLines and NSPHS. Note that DNA methylation predictors used were technical bias-adjusted, normalised residuals and thus effect sizes of the association (β) are not directly comparable to effect sizes reported elsewhere using normalised % methylation as predictor. ¶: base model (Mbase) epigenome-wide association study was covariate adjusted for age, age squared, height, squared deviation from the mean of height, sex and interaction terms of age, age squared, height and squared deviation of height with sex, education (low, medium and high), body mass index, spirometer type, study centre as well as cell composition. +: order of cohorts: ECRHS, NFBC1966, SAPALDIA, KORA, LBC1936, LifeLines and NSPHS. §: replication was defined for association if replication p<0.0011 (multiple testing correction, 47 tests for FEV1/FVC). ƒ: smoking CpGs defined on the reported FDR-corrected p<0.05 for association reported with smoking status and reported direction of effects for association with smoking [2].