TABLE 2.
Association of DNA methylation (DNAm) change with asthma acquisition from pre- to post-adolescence at 13 cytosine-phosphate-guanine (CpG) sites that are sex-specific. Significant interactions between DNAm and sex on asthma acquisition from 10 to 18 y identified in the Isle of Wight birth cohort (IOWBC)a were further tested in the Avon Longitudinal Study of Parents and Children 11(ALSPAC) cohortb. Males are in the reference group
CpG site | Est.c | IOWBC | Gene | CpG islands | Gene location | Chr.e | ALSPAC cohort | |||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Int.c | 95% CIc | P dRaw | P dFDR | Est.c | Int.c | P d Raw | ||||||
cg03269757 | −1.34 | 4.38 | 1.93, 6.83 | 1.88 × 10−4 | .02 | ATL2 | N_Shore | Body | 2 | 0.03 | 0.59 | .19 |
cg11295724 | −0.33 | 7.82 | 4.12, 11.52 | 5.35 × 10−6 | .003 | SIRPD | – | TSS200 | 20 | 0.06 | 0.76 | .22 |
cg12587133 | 0.34 | 4.85 | 2.37, 7.32 | 1.03 × 10−5 | .003 | AGA | – | 4 | 0.01 | 0.24 | .5 | |
cg15154628 | −0.67 | 3.23 | 1.14, 5.31 | 1.15 × 10−3 | .05 | CCDC146 | – | Body | 7 | 0.24 | 0.07 | .89 |
cg16301989 | −0.48 | 4.42 | 1.89, 6.93 | 1.86 × 10−4 | .02 | FUNDC2P2f | – | 2 | 0.05 | 0.47 | .26 | |
cg18278943 | 0.70 | 4.55 | 1.87, 7.24 | 4.36 × 10−4 | .03 | SLMAP | N_Shelf | 3 | −0.25 | 0.82 | .18 | |
cg20885063 | −0.52 | 4.45 | 1.86, 7.05 | 3.78 × 10−4 | .03 | ATPAF2 | N_Shelf | Body | 17 | 0.007 | 0.4 | .36 |
cg20891917 | −0.43 | 5.5 | 2.03, 8.96 | 9.86 × 10 −4 | .04s | IFRD1 | – | 5′UTR | 7 | −0.13 | 1.26 | .01 |
cg21163444 | −2.22 | 11.13 | 4.31, 17.95 | 8.53 × 10−4 | .04 | ZNF385A | S_Shore | Body | 12 | 0.27 | 0.14 | .86 |
cg22484084 | 0.29 | 7.18 | 2.69, 11.67 | 1.0 × 10−3 | .04 | PTPRV | – | TSS1500 | 1 | 0.13 | 0.84 | .39 |
cg06492287 | −1.91 | 10.49 | 4.73, 16.25 | 7.78 × 10−5 | .01 | SNTG2 | – | Body | 2 | 0.002 | −0.04 | .96 |
cg11770323 | −0.7 | 9.18 | 4.11, 14.25 | 7.92 × 10−5 | .01 | NDFIP2 | – | Body | 13 | −0.75 | −0.55 | .29 |
cg11814087 | 0.58 | 6.14 | 2.29, 10.01 | 8.85 × 10−4 | .04 | ZFR | – | Body | 5 | 0.11 | −0.68 | .05 |
For the analyses in IoW, logistic regression models were adjusted for birth weight, sex, maternal and paternal disease status of asthma, socio-economic status (SES), change of atopic status, BMI, height from 10 to 18 y.
Analyses of ALSPAC used similar covariates: maternal disease status of asthma, sex, birth weight, SES, atopy status at 7 y, and changes of height, and BMI from 7 to 15/17 y.
Est., Estimated main effect; Int., interaction coefficient of the CpGs with the sex of a child. Interaction effects consistent between the two cohorts are with bold fonts; CI, confidence interval.
PRaw, raw P-value; PFDR, adjusted P-value for multiple testing by controlling a false discovery rate (FDR) of .05. All the P-values are for interaction effects.
Chr., Chromosome.
Genes closest to the CpG site annotated using the UCSC genome browser.