{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:48:59Z","timestamp":1793508539063,"version":"4.5.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R21ES024356"],"award-info":[{"award-number":["R21ES024356"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["2R01ES010544"],"award-info":[{"award-number":["2R01ES010544"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["U54ES012078"],"award-info":[{"award-number":["U54ES012078"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Epigenet"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lead, a known neurotoxicant, has previously received attention in Parkinson\u2019s disease (PD) research, but epidemiologic studies have been limited in sample size and findings are equivocal. We generated two methylation-based biomarkers for cumulative tibia and patella bone-measured lead exposure in 1528 PD patients and 1169 controls. PD status was associated with increased levels of the DNAm biomarker for tibia-lead levels. We estimated a meta-OR for PD of 1.89 per unit DNAm tibia-lead increase (95% CI 1.59, 2.24; p\u2009=\u20098.1E\u221213). The current study supports the notion that chronic and long-term lead exposure tracked via DNAm may contribute to PD pathogenesis.<\/jats:p>","DOI":"10.1186\/s13148-021-01051-3","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T11:03:02Z","timestamp":1616410982000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["DNA methylation biomarker for cumulative lead exposure is associated with Parkinson\u2019s disease"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4476-2352","authenticated-orcid":false,"given":"Kimberly C.","family":"Paul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Horvath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irish","family":"Del Rosario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff M.","family":"Bronstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Ritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"issue":"1","key":"1051_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3233\/JAD-180267","volume":"64","author":"A Reuben","year":"2018","unstructured":"Reuben A. Childhood Lead Exposure and Adult Neurodegenerative Disease. J Alzheimer\u2019s Disease. 2018;64(1):17\u201342.","journal-title":"J Alzheimer\u2019s Disease."},{"issue":"11","key":"1051_CR2","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1289\/ehp.1002339","volume":"118","author":"MG Weisskopf","year":"2010","unstructured":"Weisskopf MG, Weuve J, Nie H, Saint-Hilaire MH, Sudarsky L, Simon DK, et al. Association of cumulative lead exposure with Parkinson\u2019s disease. Environ Health Perspect. 2010;118(11):1609\u201313.","journal-title":"Environ Health Perspect."},{"issue":"12","key":"1051_CR3","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1289\/ehp.9102","volume":"114","author":"S Coon","year":"2006","unstructured":"Coon S, Stark A, Peterson E, Gloi A, Kortsha G, Pounds J, et al. Whole-body lifetime occupational lead exposure and risk of Parkinson\u2019s disease. Environ Health Perspect. 2006;114(12):1872\u20136.","journal-title":"Environ Health Perspect."},{"issue":"3","key":"1051_CR4","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1212\/WNL.48.3.650","volume":"48","author":"JM Gorell","year":"1997","unstructured":"Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, et al. Occupational exposures to metals as risk factors for Parkinson\u2019s disease. Neurology. 1997;48(3):650\u20138.","journal-title":"Neurology"},{"issue":"5","key":"1051_CR5","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1212\/WNL.46.5.1275","volume":"46","author":"A Seidler","year":"1996","unstructured":"Seidler A, Hellenbrand W, Robra BP, Vieregge P, Nischan P, Joerg J, et al. Possible environmental, occupational, and other etiologic factors for Parkinson\u2019s disease: a case-control study in Germany. Neurology. 1996;46(5):1275\u201384.","journal-title":"Neurology"},{"issue":"3","key":"1051_CR6","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/ajim.20788","volume":"53","author":"JA Firestone","year":"2010","unstructured":"Firestone JA, Lundin JI, Powers KM, Smith-Weller T, Franklin GM, Swanson PD, et al. Occupational factors and risk of Parkinson\u2019s disease: a population-based case-control study. Am J Ind Med. 2010;53(3):217\u201323.","journal-title":"Am J Ind Med."},{"issue":"9","key":"1051_CR7","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1289\/ehp.1307218","volume":"122","author":"N Palacios","year":"2014","unstructured":"Palacios N, Fitzgerald K, Roberts AL, Hart JE, Weisskopf MG, Schwarzschild MA, et al. A prospective analysis of airborne metal exposures and risk of Parkinson disease in the nurses\u2019 health study cohort. Environ Health Perspect. 2014;122(9):933\u20138.","journal-title":"Environ Health Perspect."},{"issue":"12","key":"1051_CR8","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1093\/aje\/kwq303","volume":"172","author":"AW Willis","year":"2010","unstructured":"Willis AW, Evanoff BA, Lian M, Galarza A, Wegrzyn A, Schootman M, et al. Metal emissions and urban incident Parkinson disease: a community health study of medicare beneficiaries by using geographic information systems. Am J Epidemiol. 2010;172(12):1357\u201363.","journal-title":"Am J Epidemiol."},{"issue":"3","key":"1051_CR9","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1289\/ehp.9783","volume":"115","author":"H Hu","year":"2007","unstructured":"Hu H, Shih R, Rothenberg S, Schwartz BS. The epidemiology of lead toxicity in adults: Measuring dose and consideration of other methodologic issues. Environ Health Perspect. 2007;115(3):455\u201362.","journal-title":"Environ Health Perspect."},{"issue":"1","key":"1051_CR10","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/s41370-019-0183-9","volume":"31","author":"E Colicino","year":"2019","unstructured":"Colicino E, Just A, Kioumourtzoglou MA, Vokonas P, Cardenas A, Sparrow D, et al. Blood DNA methylation biomarkers of cumulative lead exposure in adults. J Expo Sci Environ Epidemiol. 2019;31(1):108\u201316.","journal-title":"J Expo Sci Environ Epidemiol"},{"key":"1051_CR11","doi-asserted-by":"crossref","unstructured":"Vallerga CL, Zhang F, Fowdar J, McRae AF, Qi T, Nabais MF, et al. Analysis of DNA methylation associates the cystine\u2013glutamate antiporter SLC7A11 with risk of Parkinson\u2019s disease. Nat Commun. 2020;","DOI":"10.1038\/s41467-020-15065-7"},{"issue":"1","key":"1051_CR12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1007\/s40572-016-0083-2","volume":"3","author":"BR Ritz","year":"2016","unstructured":"Ritz BR, Paul KC, Bronstein JM. Of pesticides and men: a California story of genes and environment in Parkinson\u2019s disease. Curr Environ Heal reports. 2016;3(1):40\u201352.","journal-title":"Curr Environ Heal reports."},{"issue":"1","key":"1051_CR13","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13073-017-0466-5","volume":"9","author":"Y-H Chuang","year":"2017","unstructured":"Chuang Y-H, Paul KC, Bronstein JM, Bordelon Y, Horvath S, Ritz B. Parkinson\u2019s disease is associated with DNA methylation levels in human blood and saliva. Genome Med. 2017;9(1):76.","journal-title":"Genome Med."},{"issue":"10","key":"1051_CR14","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/gb-2013-14-10-r115","volume":"14","author":"S Horvath","year":"2013","unstructured":"Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14(10):96.","journal-title":"Genome Biol."},{"key":"1051_CR15","doi-asserted-by":"crossref","unstructured":"Houseman EA, Accomando WP, Koestler DC, Christensen BC, Marsit CJ, Nelson HH, et al. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformat. 2012;","DOI":"10.1186\/1471-2105-13-86"},{"issue":"7","key":"1051_CR16","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1093\/oxfordjournals.aje.a009318","volume":"146","author":"R Kim","year":"1997","unstructured":"Kim R, Landrigan C, Mossmann P, Sparrow D, Hu H. Age and secular trends in bone lead levels in middle-aged and elderly men: three-year longitudinal follow-up in the normative aging study. Am J Epidemiol. 1997;146(7):586\u201391.","journal-title":"Am J Epidemiol."},{"key":"1051_CR17","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.parkreldis.2016.03.017","volume":"27","author":"J Koerts","year":"2016","unstructured":"Koerts J, K\u00f6nig M, Tucha L, Tucha O. Working capacity of patients with Parkinson\u2019s disease\u2014a systematic review. Parkinsonism Relat Disord. 2016;27:9\u201324.","journal-title":"Parkinsonism Relat Disord."},{"issue":"6","key":"1051_CR18","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1002\/ajim.22448","volume":"58","author":"DH Koh","year":"2015","unstructured":"Koh DH, Locke SJ, Chen YC, Purdue MP, Friesen MC. Lead exposure in US worksites: A literature review and development of an occupational lead exposure database from the published literature. Am J Ind Med. 2015;58(6):605\u201316.","journal-title":"Am J Ind Med."}],"container-title":["Clinical Epigenetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13148-021-01051-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13148-021-01051-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13148-021-01051-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T14:36:56Z","timestamp":1724683016000},"score":1,"resource":{"primary":{"URL":"https:\/\/clinicalepigeneticsjournal.biomedcentral.com\/articles\/10.1186\/s13148-021-01051-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1051"],"URL":"https:\/\/doi.org\/10.1186\/s13148-021-01051-3","relation":{},"ISSN":["1868-7075","1868-7083"],"issn-type":[{"value":"1868-7075","type":"print"},{"value":"1868-7083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"assertion":[{"value":"17 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2021","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 PEG study was approved by the UCLA Institutional Review Board (IRB# 11-001530) and informed consent was obtained from all individuals. Our research conformed to the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable, this manuscript does not contain any individual person\u2019s data in any form, e.g. individual details, images, or videos.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"59"}}