Journal article

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

Pierre-Antoine Dugue, Chenglong Yu, Timothy McKay, Ee Ming Wong, Jihoon Eric Joo, Helen Tsimiklis, Fleur Hammet, Maryam Mahmoodi, Derrick Theys, John L Hopper, Graham G Giles, Roger L Milne, Jason A Steen, James G Dowty, Tu Nguyen-Dumont, Melissa C Southey

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | MDPI | Published : 2021

Abstract

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 ..

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Grants

Awarded by U.S. National Institute of Health


Awarded by U.S. National Cancer Institute


Awarded by Australian National Health and Medical Research Council


Awarded by NHMRC


Awarded by National Breast Cancer Foundation (Australia)


Awarded by National Health and Medical Research Council (NMHRC, Australia)


Awarded by National Breast Cancer Foundation (BRA-STRAP)


Awarded by NHMRC European Union Collaborative Research Grant


Funding Acknowledgements

This work was supported by the U.S. National Institute of Health (grant number RO1CA159868). The ABCFR was supported in Australia by the National Health and Medical Research Council, the New South Wales Cancer Council, the Victorian Health Promotion Foundation, the Victorian Breast Cancer Research Consortium, Cancer Australia, and the National Breast Cancer Foundation. The six sites of the Breast Cancer Family Registry (BCFR) were supported by grant UM1 CA164920 from the U.S. National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the BCFR. The MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 251553, 504711, 396414, 1074383, and by infrastructure provided by Cancer Council Victoria. The MCCS methylation studies were supported by the NHMRC grants 1011618, 1026892, 1027505, 1050198, 1043616, 1074383 and 1164455.TN-D is a National Breast Cancer Foundation (Australia) Career Development Fellow (ECF-17-001), M.C.S. is a National Health and Medical Research Council (NMHRC, Australia) Senior Research Fellow (APP1155163). This work was supported by an NHMRC Program grant (APP1074383), The National Breast Cancer Foundation (BRA-STRAP; NT-15-016), NHMRC European Union Collaborative Research Grant (APP1101400) and Monash University, Melbourne, Australia. kConFab is supported by a grant from the National Breast Cancer Foundation and previously by the National Health and Medical Research Council (NHMRC); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; and the Cancer Foundation ofWestern Australia.