{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T07:54:47Z","timestamp":1771919687782,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1CA159868"],"award-info":[{"award-number":["RO1CA159868"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UM1 CA164920"],"award-info":[{"award-number":["UM1 CA164920"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["209057; 251553; 504711; 396414; 1074383; 1011618; 1026892; 1027505; 1050198; 1043615; 1074383; 1164455; 1155163; 1074383; 1101400"],"award-info":[{"award-number":["209057; 251553; 504711; 396414; 1074383; 1011618; 1026892; 1027505; 1050198; 1043615; 1074383; 1164455; 1155163; 1074383; 1101400"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001026","name":"National Breast Cancer Foundation","doi-asserted-by":"publisher","award":["ECF-17-001; NT-15-016"],"award-info":[{"award-number":["ECF-17-001; NT-15-016"]}],"id":[{"id":"10.13039\/501100001026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u00b1 50 kb of the most heritable CpG site) identified 43 variants associated with VTRNA2-1 methylation (p &lt; 1.5 \u00d7 10\u22124); however, these explained little of the methylation variation (R2 &lt; 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: \u22120.14 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.<\/jats:p>","DOI":"10.3390\/ijms22052535","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T20:33:57Z","timestamp":1614803637000},"page":"2535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["VTRNA2-1: Genetic Variation, Heritable Methylation and Disease Association"],"prefix":"10.3390","volume":"22","author":[{"given":"Pierre-Antoine","family":"Dugu\u00e9","sequence":"first","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"},{"name":"Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia"},{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenglong","family":"Yu","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"McKay","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ee Ming","family":"Wong","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihoon Eric","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Tsimiklis","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fleur","family":"Hammet","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Mahmoodi","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derrick","family":"Theys","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"kConFab","sequence":"additional","affiliation":[{"name":"Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L.","family":"Hopper","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham G.","family":"Giles","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"},{"name":"Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia"},{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger L.","family":"Milne","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"},{"name":"Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia"},{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason A.","family":"Steen","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James G.","family":"Dowty","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tu","family":"Nguyen-Dumont","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"},{"name":"Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-9005","authenticated-orcid":false,"given":"Melissa C.","family":"Southey","sequence":"additional","affiliation":[{"name":"Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia"},{"name":"Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC 3004, Australia"},{"name":"Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/s41467-018-03058-6","article-title":"Heritable DNA methylation marks associated with susceptibility to breast cancer","volume":"9","author":"Joo","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cell.2014.02.045","article-title":"Transgenerational epigenetic inheritance: Myths and mechanisms","volume":"157","author":"Heard","year":"2014","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1086\/598822","article-title":"Transgenerational epigenetic inheritance: Prevalence, mechanisms, and implications for the study of heredity and evolution","volume":"84","author":"Jablonka","year":"2009","journal-title":"Q. Rev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-05445-5","article-title":"A critical view on transgenerational epigenetic inheritance in humans","volume":"9","author":"Horsthemke","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1261\/rna.060269.116","article-title":"Human noncoding RNA 886 (nc886) adopts two structurally distinct conformers that are functionally opposing regulators of PKR","volume":"23","author":"Calderon","year":"2017","journal-title":"RNA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"783","DOI":"10.4161\/epi.28323","article-title":"Variable maternal methylation overlapping the nc886\/vtRNA2-1 locus is locked between hypermethylated repeats and is frequently altered in cancer","volume":"9","author":"Romanelli","year":"2014","journal-title":"Epigenetics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E11970","DOI":"10.1073\/pnas.1815005115","article-title":"Mother\u2013child transmission of epigenetic information by tunable polymorphic imprinting","volume":"115","author":"Carpenter","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","first-page":"253","article-title":"Structure and function of the protein Kinase R","volume":"Volume 316","author":"Sadler","year":"2007","journal-title":"Interferon: The 50th Anniversary"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.4049\/jimmunol.1701234","article-title":"The noncoding RNA nc886 regulates PKR signaling and cytokine production in human cells","volume":"202","author":"Golec","year":"2019","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"254","DOI":"10.20892\/j.issn.2095-3941.2017.0029","article-title":"Aberrant control of NF-\u03baB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: Molecular mode","volume":"14","author":"Vlahopoulos","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/S0168-9525(02)02709-9","article-title":"Metastable epialleles in mammals","volume":"18","author":"Rakyan","year":"2002","journal-title":"Trends Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrg2045","article-title":"Environmental epigenomics and disease susceptibility","volume":"8","author":"Jirtle","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_13","first-page":"1","article-title":"Epigenetic supersimilarity of monozygotic twin pairs","volume":"19","author":"Coarfa","year":"2018","journal-title":"Genome Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1002\/pros.23654","article-title":"Heritable methylation marks associated with breast and prostate cancer risk","volume":"78","author":"Dowty","year":"2018","journal-title":"Prostate"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13059-015-0660-y","article-title":"Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment","volume":"16","author":"Silver","year":"2015","journal-title":"Genome Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1093\/ije\/dyy032","article-title":"The long-term impact of folic acid in pregnancy on offspring DNA methylation: Follow-up of the Aberdeen Folic Acid Supplementation Trial (AFAST)","volume":"47","author":"Richmond","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"ref_17","first-page":"28","article-title":"DNA methylation in blood from neonatal screening cards and the association with BMI and insulin sensitivity in early childhood","volume":"42","author":"Peters","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Min, J.L., Hemani, G., Hannon, E., Dekkers, K.F., Castillo-Fernandez, J., Luijk, R., Carnero-Montoro, E., Lawson, D.J., Burrows, K., and Suderman, M. (2020). Genomic and phenomic insights from an atlas of genetic effects on DNA methylation. medRxiv.","DOI":"10.1101\/2020.09.01.20180406"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-35871-w","article-title":"Identification of 55,000 replicated DNA methylation QTL","volume":"8","author":"McRae","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1080\/15592294.2019.1668739","article-title":"Smoking and blood DNA methylation: An epigenome-wide association study and assessment of reversibility","volume":"15","author":"Jung","year":"2020","journal-title":"Epigenetics"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dugu\u00e9, P., Wilson, R., Lehne, B., Jayasekara, H., Wang, X., Jung, C., Joo, J.E., Makalic, E., Schmidt, D.F., and Baglietto, L. (2019). Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross-sectional and longitudinal data. Addict. Biol., e12855.","DOI":"10.1111\/adb.12855"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/ijo.2017.269","article-title":"Novel associations between blood DNA methylation and body mass index in middle-aged and older adults","volume":"42","author":"Geurts","year":"2018","journal-title":"Int. J. Obes."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e011768","DOI":"10.1136\/bmjopen-2016-011768","article-title":"Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study","volume":"6","author":"Finer","year":"2016","journal-title":"BMJ Open"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-016-0926-z","article-title":"Systematic identification of genetic influences on methylation across the human life course","volume":"17","author":"Gaunt","year":"2016","journal-title":"Genome Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R73","DOI":"10.1186\/gb-2014-15-5-r73","article-title":"Contribution of genetic variation to transgenerational inheritance of DNA methylation","volume":"15","author":"McRae","year":"2014","journal-title":"Genome Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11115","DOI":"10.1038\/ncomms11115","article-title":"Genetic and environmental influences interact with age and sex in shaping the human methylome","volume":"7","author":"Nivard","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41588-020-0609-2","article-title":"Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses","volume":"52","author":"Zhang","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature24284","article-title":"Association analysis identifies 65 new breast cancer risk loci","volume":"551","author":"Michailidou","year":"2017","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fort, R.S., Math\u00f3, C., Geraldo, M.V., Ottati, M.C., Yamashita, A.S., Saito, K.C., Leite, K.R.M., M\u00e9ndez, M., Maedo, N., and M\u00e9ndez, L. (2018). Nc886 is epigenetically repressed in prostate cancer and acts as a tumor suppressor through the inhibition of cell growth. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4049-7"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1038\/onc.2012.382","article-title":"Cell death\/proliferation roles for nc886, a non-coding RNA, in the protein kinase R pathway in cholangiocarcinoma","volume":"32","author":"Kunkeaw","year":"2013","journal-title":"Oncogene"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.18632\/oncotarget.1927","article-title":"Epigenetic silencing of the non-coding RNA nc886 provokes oncogenes during human esophageal tumorigenesis","volume":"5","author":"Lee","year":"2014","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1158\/0008-5472.CAN-12-3055","article-title":"DNA methylation-mediated repression of miR-886-3p predicts poor outcome of human small cell lung cancer","volume":"73","author":"Cao","year":"2013","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.18632\/oncotarget.2047","article-title":"nc886, a non-coding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer","volume":"5","author":"Lee","year":"2014","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1182\/blood-2011-06-362541","article-title":"Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML","volume":"119","author":"Treppendahl","year":"2012","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.12659\/MSM.900320","article-title":"Silencing nc886, a non-coding RNA, induces apoptosis of human endometrial cancer cells-1A in vitro","volume":"23","author":"Hu","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"75000","DOI":"10.18632\/oncotarget.11852","article-title":"nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in thyroid cancer","volume":"7","author":"Lee","year":"2016","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1093\/ije\/dyx085","article-title":"Cohort profile: The Melbourne collaborative cohort study (Health 2020)","volume":"46","author":"Milne","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"30317","DOI":"10.1038\/srep30317","article-title":"Reliability of DNA methylation measures from dried blood spots and mononuclear cells using the human methylation 450k bead array","volume":"6","author":"English","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1002\/ijc.30175","article-title":"Association between selected dietary scores and the risk of urothelial cell carcinoma: A prospective cohort study","volume":"139","author":"Hodge","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.3945\/jn.111.157222","article-title":"Alternative dietary indices both strongly predict risk of chronic disease","volume":"142","author":"Chiuve","year":"2012","journal-title":"J. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"463","DOI":"10.5694\/j.1326-5377.2000.tb124064.x","article-title":"kConFab: A research resource of Australasian breast cancer families","volume":"172","author":"Osborne","year":"2000","journal-title":"Med. J. Aust."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"R375","DOI":"10.1186\/bcr801","article-title":"The Breast Cancer Family Registry: An infrastructure for cooperative multinational, interdisciplinary and translational studies of the genetic epidemiology of breast cancer","volume":"6","author":"John","year":"2004","journal-title":"Breast Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1093\/ije\/dyv118","article-title":"Cohort profile: The breast cancer Prospective Family Study Cohort (ProF-SC)","volume":"45","author":"Terry","year":"2016","journal-title":"Int. J. Epidemiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: A flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1093\/nar\/gkw227","article-title":"VarDict: A novel and versatile variant caller for next-generation sequencing in cancer research","volume":"44","author":"Lai","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10689-020-00164-7","article-title":"Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer","volume":"19","author":"Steen","year":"2020","journal-title":"Fam. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1158\/1055-9965.EPI-16-0106","article-title":"The OncoArray Consortium: A network for understanding the genetic architecture of common cancers","volume":"26","author":"Amos","year":"2017","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/ng.3656","article-title":"Next-generation genotype imputation service and methods","volume":"48","author":"Das","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Howie, B.N., Donnelly, P., and Marchini, J. (2009). A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet., 5.","DOI":"10.1371\/journal.pgen.1000529"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1038\/mp.2017.153","article-title":"Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N = 112 117)","volume":"22","author":"Clarke","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1608","DOI":"10.1002\/mpr.1608","article-title":"A tutorial on conducting genome-wide association studies: Quality control and statistical analysis","volume":"27","author":"Marees","year":"2018","journal-title":"Int. J. Methods Psychiatr. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Joo, J.E., Wong, E.M., Baglietto, L., Jung, C.-H., Tsimiklis, H., Park, D.J., Wong, N.C., English, D.R., Hopper, J.L., and Severi, G. (2013). The use of DNA from archival dried blood spots with the Infinium Human Methylation 450 array. BMC Biotechnol., 13.","DOI":"10.1186\/1472-6750-13-23"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Du, P., Zhang, X., Huang, C.C., Jafari, N., Kibbe, W.A., Hou, L., and Lin, S.M. (2010). Comparison of Beta-value and M-value Methods for quantifying methylation levels by microarray analysis. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-587"},{"key":"ref_55","first-page":"235-14","article-title":"Evaluation of commonly used analysis strategies for epigenome- and transcriptome-wide association studies through replication of large-scale population studies","volume":"20","author":"Mandaviya","year":"2019","journal-title":"Genome Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-05714-3","article-title":"Autosomal genetic variation is associated with DNA methylation in regions variably escaping X-chromosome inactivation","volume":"9","author":"Luijk","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Houseman, E.A., Accomando, W.P., Koestler, D.C., Christensen, B.C., Marsit, C.J., Nelson, H.H., Wiencke, J.K., and Kelsey, K.T. (2012). DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinform., 13.","DOI":"10.1186\/1471-2105-13-86"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"R31","DOI":"10.1186\/gb-2014-15-2-r31","article-title":"Accounting for cellular heterogeneity is critical in epigenome-wide association studies","volume":"15","author":"Jaffe","year":"2014","journal-title":"Genome Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/ije\/dyp334","article-title":"Illustrating bias due to conditioning on a collider","volume":"39","author":"Cole","year":"2010","journal-title":"Int. J. Epidemiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/01.EDE.0000042804.12056.6C","article-title":"quantifying biases in causal models: Classical confounding vs collider-stratification bias","volume":"14","author":"Greenland","year":"2003","journal-title":"Epidemiology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/ije\/dyu025","article-title":"Commentary: Three worlds collide: Berkson\u2019s bias, selection bias and collider bias","volume":"43","author":"Pearce","year":"2014","journal-title":"Int. J. Epidemiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: A tool for genome-wide complex trait analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/ng.608","article-title":"Common SNPs explain a large proportion of the heritability for human height","volume":"42","author":"Yang","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nature09298","article-title":"Integrating common and rare genetic variation in diverse human populations","volume":"467","author":"Consortium","year":"2010","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/ng.2742","article-title":"Genome-wide association analysis identifies 13 new risk loci for schizophrenia","volume":"45","author":"Ripke","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ng.3406","article-title":"An atlas of genetic correlations across human diseases and traits","volume":"47","author":"Finucane","year":"2015","journal-title":"Nat. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2535\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:32:12Z","timestamp":1760160732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,3]]},"references-count":66,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22052535"],"URL":"https:\/\/doi.org\/10.3390\/ijms22052535","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,3]]}}}