Projects per year
VTRNA2‐1 is a metastable epiallele with accumulating evidence that methylation at this region is heritable, modifiable and associated with disease including risk and progression of cancer. This study investigated the influence of genetic variation and other factors such as age and adult lifestyle on blood DNA methylation in this region. We first sequenced the VTRNA2‐1 gene region in multiple‐case breast cancer families in which VTRNA2‐1 methylation was identified as heritable and associated with breast cancer risk. Methylation quantitative trait loci (mQTL) were investigated using a prospective cohort study (4500 participants with genotyping and methylation data). The cis-mQTL analysis (334 variants ± 50 kb of the most heritable CpG site) identified 43 variants associated with VTRNA2‐1 methylation (p < 1.5 × 10−4 ); however, these explained little of the methylation variation (R2 < 0.5% for each of these variants). No genetic variants elsewhere in the genome were found to strongly influence VTRNA2‐1 methylation. SNP‐based heritability estimates were consistent with the mQTL findings (h2 = 0, 95%CI: −0.14 to 0.14). We found no evidence that age, sex, country of birth, smoking, body mass index, alcohol consumption or diet influenced blood DNA methylation at VTRNA2‐1. Genetic factors and adult lifestyle play a minimal role in explaining methylation var-iability at the heritable VTRNA2‐1 cluster.
- Breast cancer
- Methylation quantitative trait loci
- Prostate cancer
- SNP‐based heritability
Precision Public Health for major cancers - novel approaches to building the genetic, epigenetic and lifestyle knowledge base for assessing risk and prognosis
Giles, G. G., Southey, M., Jenkins, M. A. & Hopper, J. L.
1/01/15 → 31/12/19