Table 2. Differentially methylated CpGs associated with age-independent CVR in the discovery, validation and metaanalysis stage using (A) the Δage approach and (B) the residuals approach, and the model adjusted for age, sex, cell type and surrogate variables.
A. Δage approach | ||||||||||||
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Features | Discovery stage (REGICOR) |
Validation stage (Framingham) |
Metaanalysis (Discovery + Validation) |
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CpG | Chr* | Position (bp) |
Gene | Coeff* | SE* | P-value | Coeff* | SE* | P-value | Coeff* | SE* | P-value |
cg12547807 | 1 | 9473751 | NA; (LOC100506022) | −2.04·10−2 | 4.53·10−3 | 6.83·10−6 | −1.60·10−2 | 2.23·10−3 | 6.91·10−13 | −1.69·10−2 | 2.00·10−3 | <2·10−16 |
cg27537125 | 1 | 25349681 | NA; (MIR4425) | −2.13·10−2 | 4.38·10−3 | 1.10·10−6 | −8.46·10−3 | 2.35·10−3 | 3.09·10−4 | −1.13·10−2 | 2.07·10−3 | 4.20·10−8 |
cg05951221 | 2 | 233284402 | NA; (AC068134.6; ALPPL2) | −2.74·10−2 | 6.14·10−3 | 8.40·10−6 | −1.07·10−2 | 3.48·10−3 | 2.02·10−3 | −1.48·10−2 | 3.03·10−3 | 1.05·10−6 |
cg21566642 | 2 | 233284661 | NA; (AC068134.6; ALPPL2) | −3.45·10−2 | 6.79·10−3 | 3.71·10−7 | −9.73·10−3 | 3.57·10−3 | 6.46·10−3 | −1.51·10−2 | 3.16·10−3 | 1.78·10−6 |
cg05575921 | 5 | 373378 | AHRR | −3.98·10−2 | 7.19·10−3 | 3.30·10−8 | −1.66·10−2 | 3.01·10−3 | 3.15·10−8 | −2.01·10−2 | 2.78·10−3 | 4.64·10−13 |
cg19939077 | 10 | 81108060 | PPIF | −1.40·10−2 | 5.59·10−3 | 1.24·10−2 | −7.12·10−3 | 2.75·10−3 | 9.71·10−3 | −8.46·10−3 | 2.47·10−3 | 6.14·10−4 |
cg00574958 | 11 | 68607622 | CPT1A | −2.01·10−2 | 5.02·10−3 | 6.21·10−5 | −1.76·10−2 | 2.88·10−3 | 9.27·10−10 | −1.82·10−2 | 2.50·10−3 | 2.82·10−13 |
cg18608055 | 19 | 1130866 | SBNO2 | −1.12·10−2 | 4.10·10−3 | 6.23·10−3 | −9.40·10−3 | 1.73·10−3 | 5.18·10−8 | −9.67·10−3 | 1.59·10−3 | 1.20·10−9 |
B. Residuals approach | ||||||||||||
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Features | Discovery stage (REGICOR) |
Validation stage (Framingham) |
Metaanalysis (Discovery+ Validation) |
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CpG | Chr* | Position (bp) |
Gene | Coeff* | SE* | P-value | Coeff* | SE* | P-value | Coeff* | SE* | P-value |
cg12547807 | 1 | 9473751 | NA; (LOC100506022) | −4.16 | 9.84·10−1 | 2.39·10−5 | −6.77 | 1.27 | 9.80·10−8 | −5.14 | 7.78·10−1 | 4.01·10−11 |
cg27537125 | 1 | 25349681 | NA; (MIR4425) | −5.30 | 1.20 | 1.07·10−5 | −4.74 | 1.23 | 1.15·10−4 | −5.03 | 8.60·10−1 | 5.14·10−9 |
cg05951221 | 2 | 233284402 | NA; (AC068134.6; ALPPL2) | −8.90 | 1.58 | 1.68·10−8 | −6.62 | 1.90 | 4.98·10−4 | −7.97 | 1.21 | 5.20·10−11 |
cg21566642 | 2 | 233284661 | NA; (AC068134.6; ALPPL2) | −8.81 | 1.59 | 3.01·10−8 | −5.90 | 1.98 | 2.85·10−3 | −7.67 | 1.24 | 6.08·10−10 |
cg05575921 | 5 | 373378 | AHRR | −8.51 | 1.84 | 3.92·10−6 | −7.08 | 1.74 | 4.60·10−5 | −7.75 | 1.26 | 8.73·10−10 |
cg19939077 | 10 | 81108060 | PPIF | −7.43 | 1.39 | 8.21·10−8 | −5.80 | 1.62 | 3.35·10−4 | −6.74 | 1.05 | 1.50·10−10 |
cg00574958 | 11 | 68607622 | CPT1A | −3.27 | 1.43 | 2.28·10−2 | −7.01 | 1.55 | 5.74·10−6 | −5.00 | 1.05 | 2.00·10−6 |
cg18608055 | 19 | 1130866 | SBNO2 | −4.83 | 1.04 | 3.55·10−6 | −4.62 | 1.03 | 7.19·10−6 | −4.72 | 7.32·10−1 | 1.11·10−10 |
CpG, CpG ID; Chr, chromosome location; Position (bp), basepair genomic position; NA, non-annotated gene; Coeff, regression coefficient; SE, standard error of the regression.