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Table 2 Results from Meta-Analyses, FEV1 and AAT, Adult Cohorts

From: SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts

CpG CpG Position Gene Group SAPALDIA Meta- Analysis of Lung Function Association in SAPALDIA, NFBC and ECRHS
Circulating AAT Cross-Sectional T1 Cross-Sectional T2 Repeat Cross-Sectional Change
Coef. P.valuea Coef. P.valuea Directionb Coef. P.valuea Directionb Coef. P.valuea Directionb Coef. P.valuea Directionb
cg10761141 94,844,776 3UTR −0.30 0.25 0.75 0.13 +++ 0.63 0.21 + − + −0.04 0.84 + − – 0.02 0.48 +++
cg25042671 94,849,061 Body −0.59 0.04 −0.72 0.25 − + − − 0.80 0.21 – − − −0.22 0.52 ++− −0.03 0.44 − + −
cg20267408 94,849,703 5UTR −0.44 0.21 −0.15 0.82 ++− −0.05 0.94 ++− 0.10 0.79 ++− 0.00 0.97 + − –
cg26938334 94,849,747 5UTR 1.16 0.42 − 0.01 0.99 − + − − 0.35 0.74 − + − − 0.33 0.34 – − + − 0.01 0.71 – – –
cg16110645 94,850,433 5UTR − 0.64 0.34 0.39 0.67 −++ 0.55 0.59 + − + 0.08 0.85 + − + −0.02 0.75 – − +
cg10832639 94,850,965 5UTR −0.25 0.72 1.24 0.16 +++ 0.01 0.99 −++ 0.18 0.61 −++ 0.00 0.95 ++−
cg02126235 94,855,034 5UTR −0.30 0.58 0.76 0.45 +++ 0.67 0.55 ++− − 0.26 0.55 – – – 0.02 0.69 ++−
cg22828990 94,855,099 5UTR −0.09 0.82 0.19 0.79 – − + 0.30 0.68 – − + 0.69 0.03 + − + −0.09 0.04 – – –
cg09968361 94,855,344 5UTR −0.33 0.44 1.43 0.04 +++ 0.65 0.36 −++ 0.72 0.02 +++ −0.10 0.01
cg13826459 94,855,505 TSS1500 −0.08 0.76 0.16 0.76 −++ 0.98 0.05 +++ −0.05 0.83 − + − 0.04 0.15 +++
cg25968219 94,855,590 TSS1500 −1.81 0.05 3.29 0.003 +++ −1.29 0.37 – − + 0.37 0.59 ++− − 0.08 0.15 – − +
cg01606800 94,855,990 TSS1500 −1.08 0.001 0.47 0.47 −++ −0.13 0.85 – − + − 0.11 0.73 – − + − 0.01 0.75 – − +
cg02181506 94,856,984 1stExon −0.78 0.08 0.11 0.89 – − + 0.65 0.40 + − + 0.28 0.47 + − + 0.02 0.71 + − –
cg10070185 94,857,151 TSS200 −0.05 0.91 0.37 0.59 – − + 1.08 0.16 +++ 0.24 0.39 −++ 0.04 0.29 + − +
cg24621042 94,857,275 TSS1500 −0.68 0.04 0.87 0.14 +++ 1.16 0.06 +++ −0.15 0.60 − + − − 0.01 0.87 + − +
cg00802237 94,858,066 TSS1500 −0.07 0.81 −0.01 0.99 + − – − 0.48 0.40 – − + 0.12 0.67 + − + −0.03 0.35 – − +
cg04179148 94,858,339 TSS1500 −0.70 0.06 1.80 0.01 +++ 0.29 0.67 +++ 0.36 0.25 +++ −0.03 0.47 – – –
  1. Cross-sectional and repeat cross-sectional models adjusted for: study center, age, age2, education, height, height2, sex, sex*age, (sex*age) 2, sex*height, (sex*height)2, Bcell, CD4T, CD8T, Eos, Mono, NK. Repeat cross-sectional in addition ran with a random intercept on the subject. In predictive models, annual change in lung function was computed as the difference between T2 and T1 divided by time of follow-up: (T2-T1)/follow-up models adjusted for covariates from T1
  2. Sample size for circulating AAT for SAPALDIA n = 561. Cross-sectional and prediction models (change) n = 1076, and n = 1122 for repeat cross-sectional models
  3. Meta-Analysis of Lung Function Association of Methylation of CpGs in the SERPINA1* Gene with FEV1 Level and Decline in Adult Ever-Smokers from SAPALDIA, ECRHS and NFBC and with Circulating AAT Concentrations in SAPALDIA
  4. From SERPINA gene cluster located on chromosome 14 between positions: 94′641’781 and 95′235’125 (human genome build 37/hg19)
  5. aNominal P-values, Bonferroni corrected significance level for 119 tests is P-value 4.6 × 10− 4
  6. bDirection of effect for SAPALDIA, ECRHS and NFBC. A positive sign indicates that an increase in methylation is associated with higher level of lung function (cross-sectional models) and with an attenuation of lung function decline, respectively (change model)
  7. Statistically significant results are highlighted in bold