Associations of age of puberty with FVC and FEV1 at age 26 years through DNA methylation at CpG sites that survived forward screening at age 18 years in the Isle of Wight birth cohort (IOWBC), further tested in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (only direction-consistent indirect effects included)
| Pubertal events (sex) | Lung function at age 26 years | CpGs | Total effect# (IOWBC) | Direct effect# (IOWBC) | Indirect effect# (IOWBC) | Total effect (ALSPAC) | Direct effect (ALSPAC) | Indirect effect (ALSPAC) | ||||||
| Est¶ | p-value¶ | Est | p-value | Est | p-value | Est | p-value | Est | p-value | Est | p-value | |||
| Menarche (female) | FVC | cg15711028 | 0.19 | 0.01 | 0.15 | 0.04 | 0.04 | 0.04 | 0.21 | 8.00×10−4 | 0.21 | 9.33×10−4 | 2.68×10−3 | 0.51 |
| cg08680129 | 0.18 | 0.01 | 0.14 | 0.06 | 0.04 | 0.03 | 0.22 | 5.62×10−4 | 0.20 | 1.28×10−3 | 1.41×10−2 | 0.15 | ||
| cg01315063 | 0.19 | 0.01 | 0.13 | 0.07 | 0.06 | 0.02 | 0.21 | 7.98×10−4 | 0.21 | 8.82×10−4 | 1.74×10−3 | 0.59 | ||
| FEV1 | cg17394530 | 0.23 | 9.22×10−4 | 0.28 | 5.54×10−5 | −0.05 | 0.02 | 0.23 | 3.61×10−4 | 0.23 | 3.44×10−4 | −4.66×10−4 | 0.90 | |
| cg08680129 | 0.24 | 5.92×10−4 | 0.20 | 0.01 | 0.05 | 0.02 | 0.23 | 3.01×10−4 | 0.22 | 5.81×10−4 | 1.02×10−2 | 0.25 | ||
| cg01315063 | 0.24 | 5.85×10−4 | 0.20 | 0.01 | 0.04 | 0.05 | 0.23 | 3.81×10−4 | 0.23 | 4.40×10−4 | 2.58×10−3 | 0.54 | ||
| cg10219771 | 0.24 | 4.91×10−4 | 0.20 | 0.01 | 0.05 | 0.03 | 0.23 | 3.97×10−4 | 0.23 | 4.03×10−4 | 1.84×10−4 | 0.95 | ||
| Body hair growth (female) | FEV1 | cg16332936 | 0.14 | 0.11 | 0.09 | 0.30 | 0.05 | 0.04 | 0.18 | 3.10×10−3 | 0.18 | 4.29×10−3 | 7.04×10−3 | 0.34 |
| cg04827020 | 0.17 | 0.04 | 0.12 | 0.16 | 0.05 | 0.03 | 0.18 | 3.30×10−3 | 0.17 | 5.91×10−3 | 1.13×10−2 | 0.17 | ||
| Body hair+ growth (male) | FVC | cg13636404 | 0.14 | 0.10 | 0.08 | 0.37 | 0.06 | 0.02 | 1.0×10−3 | 0.99 | −4.1×10−4 | 1.00 | 1.40×10−3 | 0.71 |
| cg04130455 | 0.15 | 0.08 | 0.23 | 0.01 | −0.08 | 0.01 | 3.9×10−3 | 0.95 | 0.01 | 0.93 | −1.78×10−3 | 0.83 | ||
| cg21276535 | 0.16 | 0.05 | 0.11 | 0.20 | 0.06 | 0.02 | 4.8×10−3 | 0.94 | −2.3×10−4 | 1.00 | 5.04×10−3 | 0.36 | ||
| cg27626110 | 0.11 | 0.21 | 0.17 | 0.05 | −0.06 | 0.04 | −7.3×10−4 | 0.99 | −5.6×10−4 | 0.99 | −1.70×10−4 | 0.96 | ||
| Voice deepening (male) | FVC | cg01482375 | 0.17 | 0.04 | 0.12 | 0.16 | 0.05 | 0.04 | −0.02 | 0.77 | −0.03 | 0.68 | 7.88×10−3 | 0.28 |
The complete results are in supplementary table S2A. p-values <0.05 are in bold, representing statistically significant indirect effects in IOWBC. FVC: forced vital capacity; FEV1: forced expiratory volume in 1 s; CpG: cytosine-phosphate-guanine. #: total effect is the sum of direct and indirect effects of age of pubertal events on lung function at age 26 years; indirect effect is the effect of age of pubertal events on lung function via DNA methylation at CpGs; all the effects are represented by regression coefficients. ¶: Est: regression coefficient estimates with unit in litres (L); it represents expected lung function change for 1-year increase in pubertal age. +: age at body hair growth is identified by age at attainment of Tanner stage >2 in ALSPAC cohort.