Table 2. Significant associations between tobacco smoking and methylation of lung cancer related genes in validation panel.
CpG site | Gene | Mean β value (Standard deviation) | Effect size b | Estimate (se) | p-value | FDR | |
---|---|---|---|---|---|---|---|
Never smoker | Current smoker | ||||||
cg00640087 | MSH5 | 0.165 (0.036) | 0.159 (0.035) | −0.006 | −7.4 e-3 (3.1 e-3) | 0.019 | 0.049 |
cg03281572 | VTI1A | 0.812 (0.028) | 0.793 (0.036) | −0.019 | −0.018 (3.0 e-3) | 3.8 e-7 | 1.2 e-5 |
cg07269053 | VTI1A | 0.733 (0.039) | 0.715 (0.052) | −0.018 | −0.013 (5.0 e-3) | 0.007 | 0.023 |
cg10163955 | GATA3 | 0.669 (0.043) | 0.640 (0.049) | −0.029 | −0.024 (5.1 e-3) | 5.1 e-4 | 6.6 e-5 |
cg11430077 | GATA3 | 0.147 (0.032) | 0.132 (0.029) | −0.015 | −0.013 (4.0 e-3) | 0.001 | 0.006 |
cg12324353 | TERT | 0.788 (0.032) | 0.779 (0.032) | −0.009 | −0.011 (3.5 e-3) | 0.002 | 0.011 |
cg17928584 | STK32A | 0.156 (0.053) | 0.161 (0.052) | 0.005 | 0.012 (5.0 e-3) | 0.020 | 0.049 |
cg19335412 | ACTA2 | 0.461 (0.036) | 0.451 (0.033) | −0.010 | −0.011 (4.1 e-3) | 0.009 | 0.026 |
cg19696491 | CHRNA5 | 0.470 (0.058) | 0.488 (0.060) | 0.018 | 0.018 (6.9 e-3) | 0.010 | 0.028 |
cg20640261 | MSH5 | 0.443 (0.048) | 0.424 (0.048) | −0.019 | −0.015 (5.0 e-3) | 0.003 | 0.013 |
cg22770911 | GATA3 | 0.481 (0.033) | 0.458 (0.042) | −0.023 | −0.015 (4.5 e-3) | 0.001 | 0.005 |
cg24287110 | KLF6 | 0.365 (0.056) | 0.349 (0.053) | −0.016 | −0.022 (6.0 e-3) | 6.2 e-4 | 0.005 |
cg24908166 | TERT | 0.926 (0.021) | 0.916 (0.026) | −0.010 | −0.010 (2.6 e-3) | 0.0001 | 0.001 |
Adjusted for age (years), sex, random batch effects, leukocyte distribution (Houseman algorithm [27]), alcohol consumption (abstainer/ low/ intermediate/ high), body mass index (BMI, underweight/ normal weight/ overweight/ obese), physical activity (inactive/ low/ medium or high), prevalence of cardiovascular diseases (yes/no), prevalence of diabetes (yes/no) and prevalence of cancer (yes/no)
All 31 loci identified by discovery panel were validated by the three models, and the threshold of FDR is 0.05. A total of 13 CpG sites were validated as significant smoking-related CpG sites by validation
Effect size = Mean βcurrent smoker – Mean βnever smoker