Table 4.
Methylation associated with index variants showing significant statistical interaction with cranial radiation therapy (CRT) for effect on body mass index (BMI). CpGs were identified as associated with index variants across the lifecourse in ARIES then associated with BMI in adult survivors of childhood acute lymphoblastic leukemia in the CCSS diagnosed 1970-1986.
Locus | CRT Interaction Index SNP |
CpG | CpG-SNP Distance |
ARIES meQTL (CpG-SNP) |
CCSS Cohort (CpG-Outcome) |
|||||
---|---|---|---|---|---|---|---|---|---|---|
Timepoint | Effect | P | Methylation sample | Outcome | Effect | P | ||||
SRGAP3 intron | rs730901 | cg24850121 | −43,645 | Middle Age | 0.003 | 6.3E-08 | Overall (n=96) | BMI | 0.0013 | 0.18 |
CRT treated (n=47) | BMI | −0.0005 | 0.8 | |||||||
Not CRT treated (n=49) | BMI | 0.0024 | 0.02 | |||||||
Overall (n=96) | CRT | 0.0057 | 0.6 | |||||||
UNCX-MICALL2 | rs145623412 | cg18423103 | 68,981 | Pregnancy | 0.058 | 2.1E-15 | Overall (n=96) | BMI | 0.0018 | 0.004 |
Birth | 0.002 | 5.9E-10 | CRT treated (n=47) | BMI | 0.0014 | 0.16 | ||||
Childhood | 0.009 | 3.4E-18 | Not CRT treated (n=49) | BMI | 0.0019 | 0.02 | ||||
Adolescence | 0.046 | 2.5E-19 | Overall (n=96) | CRT | 0.0015 | 0.8 | ||||
Middle Age | 0.067 | 8.0E-16 | ||||||||
UNCX-MICALL2 | rs145623412 | cg15701281 | 78,739 | Pregnancy | 0.017 | 1.7E-17 | Overall (n=96) | BMI | −0.0009 | 0.17 |
Birth | 0.023 | 1.9E-16 | CRT treated (n=47) | BMI | 0.0012 | 0.27 | ||||
Childhood | 0.008 | 1.3E-11 | Not CRT treated (n=49) | BMI | −0.0021 | 0.006 | ||||
Adolescence | 0.022 | 4.5E-15 | Overall (n=96) | CRT | 0.0006 | 0.9 | ||||
Middle Age | 0.019 | 8.2E-12 |
BMI, body mass index; CpG, cytosine-guanine dinucleotide; CRT, cranial radiation therapy; meQTL, methylation quantitative trait locus; SNP, single nucleotide polymorphism.