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Article

VTRNA2-1: Genetic Variation, Heritable Methylation and Disease Association

1
Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia
2
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia
3
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3010, Australia
4
Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC 3010, Australia
5
Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
*
Author to whom correspondence should be addressed.
Academic Editors: Maria M. Sasiadek and Pawel Karpinski
Int. J. Mol. Sci. 2021, 22(5), 2535; https://doi.org/10.3390/ijms22052535
Received: 10 February 2021 / Revised: 24 February 2021 / Accepted: 25 February 2021 / Published: 3 March 2021
(This article belongs to the Special Issue Epigenetic Mechanisms and Human Pathology)
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 variability at the heritable VTRNA2-1 cluster. View Full-Text
Keywords: VTRNA2-1; nc886; MIR886; methylation quantitative trait loci; SNP-based heritability; rs2346018; breast cancer; prostate cancer VTRNA2-1; nc886; MIR886; methylation quantitative trait loci; SNP-based heritability; rs2346018; breast cancer; prostate cancer
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MDPI and ACS Style

Dugué, P.-A.; Yu, C.; McKay, T.; Wong, E.M.; Joo, J.E.; Tsimiklis, H.; Hammet, F.; Mahmoodi, M.; Theys, D.; kConFab; Hopper, J.L.; Giles, G.G.; Milne, R.L.; Steen, J.A.; Dowty, J.G.; Nguyen-Dumont, T.; Southey, M.C. VTRNA2-1: Genetic Variation, Heritable Methylation and Disease Association. Int. J. Mol. Sci. 2021, 22, 2535. https://doi.org/10.3390/ijms22052535

AMA Style

Dugué P-A, Yu C, McKay T, Wong EM, Joo JE, Tsimiklis H, Hammet F, Mahmoodi M, Theys D, kConFab, Hopper JL, Giles GG, Milne RL, Steen JA, Dowty JG, Nguyen-Dumont T, Southey MC. VTRNA2-1: Genetic Variation, Heritable Methylation and Disease Association. International Journal of Molecular Sciences. 2021; 22(5):2535. https://doi.org/10.3390/ijms22052535

Chicago/Turabian Style

Dugué, Pierre-Antoine, Chenglong Yu, Timothy McKay, Ee M. Wong, Jihoon E. Joo, Helen Tsimiklis, Fleur Hammet, Maryam Mahmoodi, Derrick Theys, kConFab, John L. Hopper, Graham G. Giles, Roger L. Milne, Jason A. Steen, James G. Dowty, Tu Nguyen-Dumont, and Melissa C. Southey 2021. "VTRNA2-1: Genetic Variation, Heritable Methylation and Disease Association" International Journal of Molecular Sciences 22, no. 5: 2535. https://doi.org/10.3390/ijms22052535

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