{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:58:22Z","timestamp":1787828302796,"version":"build-2784847793"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100019540","name":"Natural Science Fund for Distinguished Young Scholars of Zhejiang Province","doi-asserted-by":"crossref","award":["LR22H260001"],"award-info":[{"award-number":["LR22H260001"]}],"id":[{"id":"10.13039\/501100019540","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CRUK Career Development Fellowship","award":["C31250\/A22804"],"award-info":[{"award-number":["C31250\/A22804"]}]},{"name":"Academy of Medical Sciences\/the Wellcome Trust\/ the Government Department of Business, Energy and Industrial Strategy\/the British Heart Foundation\/Diabetes UK Springboard Award","award":["SBF006\\1109"],"award-info":[{"award-number":["SBF006\\1109"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Epidemiol"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alcohol intake is thought to be a risk factor for breast cancer, but the causal relationship and carcinogenic mechanisms are not clear. We performed an up-to-date meta-analysis of prospective studies to assess observational association, and then conducted MR analysis to make causal inference based on the genetic predisposition to alcohol consumption (\u201cdrinks per week\u201d) and pathological drinking behaviours (\u201calcohol use disorder\u201d and \u201cproblematic alcohol use\u201d), as well as genetically predicted DNA methylation at by alcohol-related CpG sites in blood. We found an observational dose\u2013response association between alcohol intake and breast cancer incidence with an additional risk of 4% for per 10\u00a0g\/day increase in alcohol consumption. Genetic predisposition to alcohol consumption (\u201cdrinks per week\u201d) was not causally associated with breast cancer incidence at the OR of 1.01 (95% CI 0.84, 1.23), but problematic alcohol use (PAU) was linked to a higher breast cancer risk at the OR of 1.76 (95% CI 1.04, 2.99) when conditioning on alcohol consumption. Epigenetic MR analysis identified four CpG sites, cg03260624 near <jats:italic>CDC7<\/jats:italic> gene, cg10816169 near <jats:italic>ZNF318<\/jats:italic> gene, cg03345232 near <jats:italic>RIN3<\/jats:italic> gene, and cg26312998 near <jats:italic>RP11-867G23.13<\/jats:italic> gene, where genetically predicted epigenetic modifications were associated with an increased breast cancer incidence risk. Our findings re-affirmed that alcohol consumption is of high risk for breast cancer incidence even at a very low dose, and the pathogenic effect of alcohol on breast cancer could be due to pathological drinking behaviour and epigenetic modification at several CpG sites, which could be potential intervention targets for breast cancer prevention.<\/jats:p>","DOI":"10.1007\/s10654-022-00886-1","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T12:12:54Z","timestamp":1655381574000},"page":"701-712","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Alcohol consumption, blood DNA methylation and breast cancer: a Mendelian randomisation study"],"prefix":"10.1007","volume":"37","author":[{"given":"Xuan","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanghong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athina","family":"Spiliopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Timofeeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhou","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haomin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evropi","family":"Theodoratou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-2577","authenticated-orcid":false,"given":"Xue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"issue":"3","key":"886_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209\u201349. https:\/\/doi.org\/10.3322\/caac.21660.","journal-title":"CA Cancer J Clin"},{"key":"886_CR2","unstructured":"World Cancer Research Fund\/American Institute for Cancer Research. Continuous Update Project Expert Report 2018. Diet, nutrition, physical activity and breast cancer. dietandcancerreport.org. Accessed 2 June 2021."},{"issue":"3","key":"886_CR3","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1093\/ije\/dyv156","volume":"45","author":"S Jung","year":"2016","unstructured":"Jung S, Wang M, Anderson K, et al. Alcohol consumption and breast cancer risk by estrogen receptor status: in a pooled analysis of 20 studies. Int J Epidemiol. 2016;45(3):916\u201328. https:\/\/doi.org\/10.1093\/ije\/dyv156.","journal-title":"Int J Epidemiol"},{"issue":"5","key":"886_CR4","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1158\/1055-9965.EPI-16-0792","volume":"26","author":"LA Williams","year":"2017","unstructured":"Williams LA, Olshan AF, Hong CC, et al. Alcohol intake and breast cancer risk in African American Women from the AMBER Consortium. Cancer Epidemiol Biomark Prev. 2017;26(5):787\u201394. https:\/\/doi.org\/10.1158\/1055-9965.EPI-16-0792.","journal-title":"Cancer Epidemiol Biomark Prev"},{"issue":"8","key":"886_CR5","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1002\/ijc.31575","volume":"143","author":"ML Baglia","year":"2018","unstructured":"Baglia ML, Cook LS, Mei-Tzu C, et al. Alcohol, smoking, and risk of Her2-overexpressing and triple-negative breast cancer relative to estrogen receptor-positive breast cancer. Int J Cancer. 2018;143(8):1849\u201357. https:\/\/doi.org\/10.1002\/ijc.31575.","journal-title":"Int J Cancer"},{"key":"886_CR6","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.cancergen.2020.06.001","volume":"245","author":"J Zhu","year":"2020","unstructured":"Zhu J, Jiang X, Niu Z. Alcohol consumption and risk of breast and ovarian cancer: a Mendelian randomization study. Cancer Genet. 2020;245:35\u201341. https:\/\/doi.org\/10.1016\/j.cancergen.2020.06.001.","journal-title":"Cancer Genet"},{"issue":"2","key":"886_CR7","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/s41588-018-0307-5","volume":"51","author":"M Liu","year":"2019","unstructured":"Liu M, Jiang Y, Wedow R, et al. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nat Genet. 2019;51(2):237\u201344. https:\/\/doi.org\/10.1038\/s41588-018-0307-5.","journal-title":"Nat Genet"},{"issue":"7","key":"886_CR8","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1038\/s41593-020-0643-5","volume":"23","author":"H Zhou","year":"2020","unstructured":"Zhou H, Sealock JM, Sanchez-Roige S, et al. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nat Neurosci. 2020;23(7):809\u201318. https:\/\/doi.org\/10.1038\/s41593-020-0643-5.","journal-title":"Nat Neurosci"},{"issue":"2","key":"886_CR9","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/mp.2016.192","volume":"23","author":"C Liu","year":"2018","unstructured":"Liu C, Marioni RE, Hedman \u00c5K, et al. A DNA methylation biomarker of alcohol consumption. Mol Psychiatry. 2018;23(2):422\u201333. https:\/\/doi.org\/10.1038\/mp.2016.192.","journal-title":"Mol Psychiatry"},{"issue":"6","key":"886_CR10","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1093\/aje\/kwz032","volume":"188","author":"LE Wilson","year":"2019","unstructured":"Wilson LE, Xu Z, Harlid S, et al. Alcohol and DNA methylation: an epigenome-wide association study in blood and normal breast tissue. Am J Epidemiol. 2019;188(6):1055\u201365. https:\/\/doi.org\/10.1093\/aje\/kwz032.","journal-title":"Am J Epidemiol"},{"issue":"1","key":"886_CR11","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s13058-019-1145-9","volume":"21","author":"C Bodelon","year":"2019","unstructured":"Bodelon C, Ambatipudi S, Dugue PA, et al. Blood DNA methylation and breast cancer risk: a meta-analysis of four prospective cohort studies. Breast Cancer Res. 2019;21(1):62. https:\/\/doi.org\/10.1186\/s13058-019-1145-9.","journal-title":"Breast Cancer Res"},{"issue":"3","key":"886_CR12","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1093\/alcalc\/agaa012","volume":"55","author":"Q Sun","year":"2020","unstructured":"Sun Q, Xie W, Wang Y, et al. Alcohol consumption by beverage type and risk of breast cancer: a dose-response meta-analysis of prospective cohort studies. Alcohol Alcohol. 2020;55(3):246\u201353. https:\/\/doi.org\/10.1093\/alcalc\/agaa012.","journal-title":"Alcohol Alcohol"},{"key":"886_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0926-z","author":"TR Gaunt","year":"2016","unstructured":"Gaunt TR, Shihab HA, Hemani G, et al. Systematic identification of genetic influences on methylation across the human life course. Genome Biol. 2016. https:\/\/doi.org\/10.1186\/s13059-016-0926-z.","journal-title":"Genome Biol"},{"issue":"1","key":"886_CR14","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/ije\/dys064","volume":"42","author":"A Boyd","year":"2013","unstructured":"Boyd A, Golding J, Macleod J, et al. Cohort profile: the \u2019children of the 90s\u2019\u2014the index offspring of the Avon Longitudinal Study of parents and children. Int J Epidemiol. 2013;42(1):111\u201327. https:\/\/doi.org\/10.1093\/ije\/dys064.","journal-title":"Int J Epidemiol"},{"issue":"1","key":"886_CR15","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1093\/ije\/dys066","volume":"42","author":"A Fraser","year":"2013","unstructured":"Fraser A, Macdonald-Wallis C, Tilling K, et al. Cohort profile: the Avon Longitudinal Study of parents and children: ALSPAC mothers cohort. Int J Epidemiol. 2013;42(1):97\u2013110. https:\/\/doi.org\/10.1093\/ije\/dys066.","journal-title":"Int J Epidemiol"},{"issue":"4","key":"886_CR16","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1093\/ije\/dyv072","volume":"44","author":"CL Relton","year":"2015","unstructured":"Relton CL, Gaunt T, McArdle W, et al. Data resource profile: accessible resource for integrated epigenomic studies (ARIES). Int J Epidemiol. 2015;44(4):1181\u201390. https:\/\/doi.org\/10.1093\/ije\/dyv072.","journal-title":"Int J Epidemiol"},{"issue":"10","key":"886_CR17","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1093\/bioinformatics\/bts163","volume":"28","author":"AA Shabalin","year":"2012","unstructured":"Shabalin AA. Matrix eQTL: ultra fast eQTL analysis via large matrix operations. Bioinformatics. 2012;28(10):1353\u20138. https:\/\/doi.org\/10.1093\/bioinformatics\/bts163.","journal-title":"Bioinformatics"},{"issue":"19","key":"886_CR18","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1093\/jnci\/djj374","volume":"98","author":"Consortium TBCA","year":"2006","unstructured":"Consortium TBCA. Commonly studied single-nucleotide polymorphisms and breast cancer: results from the Breast Cancer Association Consortium. J Natl Cancer Inst. 2006;98(19):1382\u201396. https:\/\/doi.org\/10.1093\/jnci\/djj374.","journal-title":"J Natl Cancer Inst"},{"issue":"6","key":"886_CR19","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41588-020-0609-2","volume":"52","author":"H Zhang","year":"2020","unstructured":"Zhang H, Ahearn TU, Lecarpentier J, et al. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses. Nat Genet. 2020;52(6):572\u201381. https:\/\/doi.org\/10.1038\/s41588-020-0609-2.","journal-title":"Nat Genet"},{"issue":"2","key":"886_CR20","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","volume":"44","author":"J Bowden","year":"2015","unstructured":"Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512\u201325. https:\/\/doi.org\/10.1093\/ije\/dyv080.","journal-title":"Int J Epidemiol"},{"issue":"7","key":"886_CR21","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1007\/s10654-015-0011-z","volume":"30","author":"S Burgess","year":"2015","unstructured":"Burgess S, Scott RA, Timpson NJ, Davey Smith G, Thompson SG, Consortium E-I. Using published data in Mendelian randomization: a blueprint for efficient identification of causal risk factors. Eur J Epidemiol. 2015;30(7):543\u201352. https:\/\/doi.org\/10.1007\/s10654-015-0011-z.","journal-title":"Eur J Epidemiol"},{"issue":"5","key":"886_CR22","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","volume":"50","author":"M Verbanck","year":"2018","unstructured":"Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693\u20138. https:\/\/doi.org\/10.1038\/s41588-018-0099-7.","journal-title":"Nat Genet"},{"key":"886_CR23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","author":"G Hemani","year":"2018","unstructured":"Hemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018. https:\/\/doi.org\/10.7554\/eLife.34408.","journal-title":"Elife"},{"issue":"20","key":"886_CR24","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.1093\/bioinformatics\/btw373","volume":"32","author":"JR Staley","year":"2016","unstructured":"Staley JR, Blackshaw J, Kamat MA, et al. PhenoScanner: a database of human genotype-phenotype associations. Bioinformatics. 2016;32(20):3207\u20139. https:\/\/doi.org\/10.1093\/bioinformatics\/btw373.","journal-title":"Bioinformatics"},{"issue":"5","key":"886_CR25","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1093\/ije\/dyt179","volume":"42","author":"MJ Brion","year":"2013","unstructured":"Brion MJ, Shakhbazov K, Visscher PM. Calculating statistical power in Mendelian randomization studies. Int J Epidemiol. 2013;42(5):1497\u2013501. https:\/\/doi.org\/10.1093\/ije\/dyt179.","journal-title":"Int J Epidemiol"},{"issue":"1","key":"886_CR26","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12916-018-1065-z","volume":"16","author":"SC Larsson","year":"2018","unstructured":"Larsson SC, Burgess S, Micha\u00eblsson K. Serum magnesium levels and risk of coronary artery disease: Mendelian randomisation study. BMC Med. 2018;16(1):68. https:\/\/doi.org\/10.1186\/s12916-018-1065-z.","journal-title":"BMC Med"},{"issue":"6","key":"886_CR27","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1002\/ijc.33308","volume":"148","author":"J-S Ong","year":"2021","unstructured":"Ong J-S, Derks EM, Eriksson M, et al. Evaluating the role of alcohol consumption in breast and ovarian cancer susceptibility using population-based cohort studies and two-sample Mendelian randomization analyses. Int J Cancer. 2021;148(6):1338\u201350. https:\/\/doi.org\/10.1002\/ijc.33308.","journal-title":"Int J Cancer"},{"issue":"1","key":"886_CR28","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/s0378-1119(98)00094-8","volume":"211","author":"GF Hess","year":"1998","unstructured":"Hess GF, Drong RF, Weiland KL, Slightom JL, Sclafani RA, Hollingsworth RE. A human homolog of the yeast CDC7 gene is overexpressed in some tumors and transformed cell lines. Gene. 1998;211(1):133\u201340. https:\/\/doi.org\/10.1016\/s0378-1119(98)00094-8.","journal-title":"Gene"},{"issue":"4","key":"886_CR29","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.2353\/ajpath.2010.100421","volume":"177","author":"S Rodriguez-Acebes","year":"2010","unstructured":"Rodriguez-Acebes S, Proctor I, Loddo M, et al. Targeting DNA replication before it starts: Cdc7 as a therapeutic target in p53-mutant breast cancers. Am J Pathol. 2010;177(4):2034\u201345. https:\/\/doi.org\/10.2353\/ajpath.2010.100421.","journal-title":"Am J Pathol"},{"issue":"2","key":"886_CR30","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.canlet.2013.05.008","volume":"337","author":"AN Cheng","year":"2013","unstructured":"Cheng AN, Jiang SS, Fan C-C, et al. Increased Cdc7 expression is a marker of oral squamous cell carcinoma and overexpression of Cdc7 contributes to the resistance to DNA-damaging agents. Cancer Lett. 2013;337(2):218\u201325. https:\/\/doi.org\/10.1016\/j.canlet.2013.05.008.","journal-title":"Cancer Lett"},{"key":"886_CR31","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s13000-015-0360-7","volume":"10","author":"N Melling","year":"2015","unstructured":"Melling N, Muth J, Simon R, et al. Cdc7 overexpression is an independent prognostic marker and a potential therapeutic target in colorectal cancer. Diagn Pathol. 2015;10:125. https:\/\/doi.org\/10.1186\/s13000-015-0360-7.","journal-title":"Diagn Pathol"},{"issue":"4","key":"886_CR32","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.bbrc.2005.04.024","volume":"331","author":"M Ishizuka","year":"2005","unstructured":"Ishizuka M, Kawate H, Takayanagi R, Ohshima H, Tao RH, Hagiwara H. A zinc finger protein TZF is a novel corepressor of androgen receptor. Biochem Biophys Res Commun. 2005;331(4):1025\u201331. https:\/\/doi.org\/10.1016\/j.bbrc.2005.04.024.","journal-title":"Biochem Biophys Res Commun"},{"key":"886_CR33","doi-asserted-by":"publisher","first-page":"17071","DOI":"10.1038\/cddiscovery.2017.71","volume":"3","author":"M Cassandri","year":"2017","unstructured":"Cassandri M, Smirnov A, Novelli F, et al. Zinc-finger proteins in health and disease. Cell Death Discov. 2017;3:17071. https:\/\/doi.org\/10.1038\/cddiscovery.2017.71.","journal-title":"Cell Death Discov"},{"issue":"Pt 20","key":"886_CR34","doi-asserted-by":"publisher","first-page":"4159","DOI":"10.1242\/jcs.00718","volume":"116","author":"H Kajiho","year":"2003","unstructured":"Kajiho H, Saito K, Tsujita K, et al. RIN3: a novel Rab5 GEF interacting with amphiphysin II involved in the early endocytic pathway. J Cell Sci. 2003;116(Pt 20):4159\u201368. https:\/\/doi.org\/10.1242\/jcs.00718.","journal-title":"J Cell Sci"},{"issue":"4","key":"886_CR35","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1111\/tra.12547","volume":"19","author":"W Xu","year":"2018","unstructured":"Xu W, Fang F, Ding J, Wu C. Dysregulation of Rab5-mediated endocytic pathways in Alzheimer\u2019s disease. Traffic. 2018;19(4):253\u201362. https:\/\/doi.org\/10.1111\/tra.12547.","journal-title":"Traffic"},{"issue":"6","key":"886_CR36","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/s00223-019-00530-3","volume":"104","author":"R Ridder","year":"2019","unstructured":"Ridder R, Boudin E, Vandeweyer G, et al. Genetic variation in RIN3 in the Belgian population supports its involvement in the pathogenesis of paget\u2019s disease of bone and modifies the age of onset. Calcif Tissue Int. 2019;104(6):613\u201321. https:\/\/doi.org\/10.1007\/s00223-019-00530-3.","journal-title":"Calcif Tissue Int"},{"issue":"2","key":"886_CR37","doi-asserted-by":"publisher","first-page":"183","DOI":"10.4149\/202_15090N474","volume":"63","author":"S Kontsekova","year":"2016","unstructured":"Kontsekova S, Polcicova K, Takacova M, Pastorekova S. Endosialin: molecular and functional links to tumor angiogenesis. Neoplasma. 2016;63(2):183\u201392. https:\/\/doi.org\/10.4149\/202_15090N474.","journal-title":"Neoplasma"},{"issue":"1","key":"886_CR38","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s10637-017-0530-4","volume":"36","author":"SP D'Angelo","year":"2018","unstructured":"D\u2019Angelo SP, Hamid OA, Tarhini A, et al. A phase 2 study of ontuxizumab, a monoclonal antibody targeting endosialin, in metastatic melanoma. Invest New Drugs. 2018;36(1):103\u201313. https:\/\/doi.org\/10.1007\/s10637-017-0530-4.","journal-title":"Invest New Drugs"},{"issue":"2","key":"886_CR39","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1158\/1078-0432.Ccr-17-1558","volume":"24","author":"A Grothey","year":"2018","unstructured":"Grothey A, Strosberg JR, Renfro LA, et al. A randomized, double-blind, placebo-controlled phase II study of the efficacy and safety of monotherapy ontuxizumab (MORAb-004) plus best supportive care in patients with chemorefractory metastatic colorectal cancer. Clin Cancer Res. 2018;24(2):316\u201325. https:\/\/doi.org\/10.1158\/1078-0432.Ccr-17-1558.","journal-title":"Clin Cancer Res"},{"issue":"14","key":"886_CR40","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1002\/cncr.32084","volume":"125","author":"RL Jones","year":"2019","unstructured":"Jones RL, Chawla SP, Attia S, et al. A phase 1 and randomized controlled phase 2 trial of the safety and efficacy of the combination of gemcitabine and docetaxel with ontuxizumab (MORAb-004) in metastatic soft-tissue sarcomas. Cancer. 2019;125(14):2445\u201354. https:\/\/doi.org\/10.1002\/cncr.32084.","journal-title":"Cancer"},{"issue":"11","key":"886_CR41","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.1681\/ASN.2016010098","volume":"27","author":"P Sekula","year":"2016","unstructured":"Sekula P, Del Greco MF, Pattaro C, Kottgen A. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27(11):3253\u201365. https:\/\/doi.org\/10.1681\/ASN.2016010098.","journal-title":"J Am Soc Nephrol"}],"container-title":["European Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-022-00886-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10654-022-00886-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10654-022-00886-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T22:38:32Z","timestamp":1658961512000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10654-022-00886-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,16]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["886"],"URL":"https:\/\/doi.org\/10.1007\/s10654-022-00886-1","relation":{},"ISSN":["0393-2990","1573-7284"],"issn-type":[{"value":"0393-2990","type":"print"},{"value":"1573-7284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,16]]},"assertion":[{"value":"25 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"The study was performed in accordance with the Declaration of Helsinki. All cited genome-wide association studies, epigenome-wide association study and summary-level data had been approved by a relevant review board.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}