{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T17:52:55Z","timestamp":1794073975670,"version":"4.8.0"},"reference-count":93,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001922","name":"DH | NIHR | Efficacy and Mechanism Evaluation Programme","doi-asserted-by":"publisher","award":["ZIA000242"],"award-info":[{"award-number":["ZIA000242"]}],"id":[{"id":"10.13039\/501100001922","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alcohol misuse is common in many societies worldwide and is associated with extensive morbidity and mortality, often leading to alcohol use disorders (AUD) and alcohol-related end-organ damage. The underlying mechanisms contributing to the development of AUD are largely unknown; however, growing evidence suggests that alcohol consumption is strongly associated with alterations in DNA methylation. Identification of alcohol-associated methylomic variation might provide novel insights into pathophysiology and novel treatment targets for AUD. Here we performed the largest single-cohort epigenome-wide association study (EWAS) of alcohol consumption to date (<jats:italic>N<\/jats:italic>\u2009=\u20098161) and cross-validated findings in AUD populations with relevant endophenotypes, as well as alcohol-related animal models. Results showed 2504 CpGs significantly associated with alcohol consumption (Bonferroni <jats:italic>p<\/jats:italic> value &lt; 6.8\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>) with the five leading probes located in <jats:italic>SLC7A11<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u20097.75\u2009\u00d7\u200910<jats:sup>\u2212108<\/jats:sup>)<jats:italic>, JDP2<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u20091.44\u2009\u00d7\u200910<jats:sup>\u221256<\/jats:sup>)<jats:italic>, GAS5<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u20092.71\u2009\u00d7\u200910<jats:sup>\u221247<\/jats:sup>)<jats:italic>, TRA2B<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u20093.54\u2009\u00d7\u200910<jats:sup>\u221242<\/jats:sup>), and <jats:italic>SLC43A1<\/jats:italic> (<jats:italic>p<\/jats:italic>\u2009=\u20091.18\u2009\u00d7\u200910<jats:sup>\u221240<\/jats:sup>). Genes annotated to associated CpG sites are implicated in liver and brain function, the cellular response to alcohol and alcohol-associated diseases, including hypertension and Alzheimer\u2019s disease. Two-sample Mendelian randomization confirmed the causal relationship of consumption on AUD risk (inverse variance weighted (IVW) <jats:italic>p<\/jats:italic>\u2009=\u20095.37\u2009\u00d7\u200910<jats:sup>\u221209<\/jats:sup>). A methylation-based predictor of alcohol consumption was able to discriminate AUD cases in two independent cohorts (<jats:italic>p<\/jats:italic>\u2009=\u20096.32\u2009\u00d7\u200910<jats:sup>\u221238<\/jats:sup> and <jats:italic>p<\/jats:italic>\u2009=\u20095.41\u2009\u00d7\u200910<jats:sup>\u221214<\/jats:sup>). The top EWAS probe cg06690548, located in the cystine\/glutamate transporter SLC7A11, was replicated in an independent cohort of AUD and control participants (<jats:italic>N<\/jats:italic>\u2009=\u2009615) and showed strong hypomethylation in AUD (<jats:italic>p<\/jats:italic>\u2009&lt;\u200910<jats:sup>\u221217<\/jats:sup>). Decreased CpG methylation at this probe was consistently associated with clinical measures including increased heavy drinking days (<jats:italic>p<\/jats:italic>\u2009&lt;\u200910<jats:sup>\u22124<\/jats:sup>), increased liver function enzymes (GGT (<jats:italic>p<\/jats:italic>\u2009=\u20091.03\u2009\u00d7\u200910<jats:sup>\u221221<\/jats:sup>), ALT (<jats:italic>p<\/jats:italic>\u2009=\u20091.29\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>), and AST (<jats:italic>p<\/jats:italic>\u2009=\u20091.97\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>)) in individuals with AUD. Postmortem brain analyses documented increased <jats:italic>SLC7A11<\/jats:italic> expression in the frontal cortex of individuals with AUD and animal models showed marked increased expression in liver, suggesting a mechanism by which alcohol leads to hypomethylation-induced overexpression of SLC7A11. Taken together, our EWAS discovery sample and subsequent validation of the top probe in AUD suggest a strong role of abnormal glutamate signaling mediated by methylomic variation in SLC7A11. Our data are intriguing given the prominent role of glutamate signaling in brain and liver and might provide an important target for therapeutic intervention.<\/jats:p>","DOI":"10.1038\/s41380-021-01378-6","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T07:03:31Z","timestamp":1638428611000},"page":"1754-1764","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Epigenome-wide association study of alcohol consumption in N\u2009=\u20098161 individuals and relevance to alcohol use disorder pathophysiology: identification of the cystine\/glutamate transporter SLC7A11 as a top target"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0480-7755","authenticated-orcid":false,"given":"Falk W.","family":"Lohoff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni-Kim","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary A.","family":"Kaminsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie M.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mairead L.","family":"Bermingham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeesun","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart W.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rosoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0198-5078","authenticated-orcid":false,"given":"Archie","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miruna","family":"Barbu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Charlet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3599-6018","authenticated-orcid":false,"given":"Mark","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisoo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6005-1972","authenticated-orcid":false,"given":"David M.","family":"Howard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma M.","family":"O\u2019Connell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4505-8869","authenticated-orcid":false,"given":"Heather","family":"Whalley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-6106","authenticated-orcid":false,"given":"David J.","family":"Porteous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0198-4588","authenticated-orcid":false,"given":"Andrew M.","family":"McIntosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7884-5877","authenticated-orcid":false,"given":"Kathryn L.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"1378_CR1","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1001\/jamapsychiatry.2017.2161","volume":"74","author":"BF Grant","year":"2017","unstructured":"Grant BF, Chou SP, Saha TD, Pickering RP, Kerridge BT, Ruan WJ, et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001-2002 to 2012-2013: results From the National Epidemiologic Survey on Alcohol and Related Conditions. JAMA Psychiatry. 2017;74:911\u201323.","journal-title":"JAMA Psychiatry"},{"key":"1378_CR2","first-page":"6","volume":"35","author":"S Zakhari","year":"2013","unstructured":"Zakhari S. Alcohol metabolism and epigenetics changes. Alcohol Res. 2013;35:6\u201316.","journal-title":"Alcohol Res"},{"key":"1378_CR3","doi-asserted-by":"publisher","first-page":"G178","DOI":"10.1152\/ajpgi.2000.279.1.G178","volume":"279","author":"SC Lu","year":"2000","unstructured":"Lu SC, Huang ZZ, Yang H, Mato JM, Avila MA, Tsukamoto H. Changes in methionine adenosyltransferase and S-adenosylmethionine homeostasis in alcoholic rat liver. Am J Physiol Gastrointest Liver Physiol. 2000;279:G178\u2013185.","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"1378_CR4","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.alcohol.2005.03.012","volume":"35","author":"JB Mason","year":"2005","unstructured":"Mason JB, Choi SW. Effects of alcohol on folate metabolism: implications for carcinogenesis. Alcohol. 2005;35:235\u201341.","journal-title":"Alcohol"},{"key":"1378_CR5","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1159\/000449486","volume":"23","author":"A Jangra","year":"2016","unstructured":"Jangra A, Sriram CS, Pandey S, Choubey P, Rajput P, Saroha B, et al. Epigenetic modifications, alcoholic brain and potential drug targets. Ann Neurosci. 2016;23:246\u201360.","journal-title":"Ann Neurosci"},{"key":"1378_CR6","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1111\/j.1530-0277.1991.tb00536.x","volume":"15","author":"AJ Garro","year":"1991","unstructured":"Garro AJ, McBeth DL, Lima V, Lieber CS. Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol Clin Exp Res. 1991;15:395\u20138.","journal-title":"Alcohol Clin Exp Res"},{"key":"1378_CR7","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1111\/j.1530-0277.2010.01349.x","volume":"35","author":"CH Chen","year":"2011","unstructured":"Chen CH, Pan CH, Chen CC, Huang MC. Increased oxidative DNA damage in patients with alcohol dependence and its correlation with alcohol withdrawal severity. Alcohol Clin Exp Res. 2011;35:338\u201344.","journal-title":"Alcohol Clin Exp Res"},{"key":"1378_CR8","doi-asserted-by":"crossref","unstructured":"Liang X, Justice AC, So-Armah K, Krystal JH, Sinha R, Xu K. DNA methylation signature on phosphatidylethanol, not on self-reported alcohol consumption, predicts hazardous alcohol consumption in two distinct populations. Mol Psychiatry. 2021;26:2238\u201353.","DOI":"10.1038\/s41380-020-0668-x"},{"key":"1378_CR9","doi-asserted-by":"publisher","first-page":"e12855","DOI":"10.1111\/adb.12855","volume":"26","author":"PA Dugue","year":"2021","unstructured":"Dugue PA, Wilson R, Lehne B, Jayasekara H, Wang X, Jung CH, et al. Alcohol consumption is associated with widespread changes in blood DNA methylation: analysis of cross-sectional and longitudinal data. Addiction Biol. 2021;26:e12855.","journal-title":"Addiction Biol"},{"key":"1378_CR10","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1111\/acer.14168","volume":"43","author":"K Xu","year":"2019","unstructured":"Xu K, Montalvo-Ortiz JL, Zhang X, Southwick SM, Krystal JH, Pietrzak RH, et al. Epigenome-wide DNA methylation association analysis identified novel loci in peripheral cells for alcohol consumption among European American male veterans. Alcohol Clin Exp Res. 2019;43:2111\u201321.","journal-title":"Alcohol Clin Exp Res"},{"key":"1378_CR11","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, White AJ, Troester MA, Sandler DP, et al. Alcohol and DNA methylation: an epigenome-wide association study in blood and normal breast tissue. Am J Epidemiol. 2019;188:1055\u201365.","journal-title":"Am J Epidemiol"},{"key":"1378_CR12","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, Pfeiffer L, Tsai PC, Reynolds LM, et al. A DNA methylation biomarker of alcohol consumption. Mol Psychiatry. 2018;23:422\u201333.","journal-title":"Mol Psychiatry"},{"key":"1378_CR13","doi-asserted-by":"crossref","unstructured":"Lohoff FW, Roy A, Jung J, Longley M, Rosoff DB, Luo A, et al. Epigenome-wide association study and multi-tissue replication of individuals with alcohol use disorder: evidence for abnormal glucocorticoid signaling pathway gene regulation. Mol Psychiatry. 2021;26:2224\u201337.","DOI":"10.1038\/s41380-020-0734-4"},{"key":"1378_CR14","doi-asserted-by":"crossref","unstructured":"Witt SH, Frank J, Frischknecht U, Treutlein J, Streit F, Foo JC, et al. Acute alcohol withdrawal and recovery in men lead to profound changes in DNA methylation profiles: a longitudinal clinical study. Addiction. 2020;115:2034\u201344.","DOI":"10.1111\/add.15020"},{"key":"1378_CR15","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1038\/mp.2017.168","volume":"23","author":"FW Lohoff","year":"2018","unstructured":"Lohoff FW, Sorcher JL, Rosen AD, Mauro KL, Fanelli RR, Momenan R, et al. Methylomic profiling and replication implicates deregulation of PCSK9 in alcohol use disorder. Mol Psychiatry. 2018;23:1900\u201310.","journal-title":"Mol Psychiatry"},{"key":"1378_CR16","doi-asserted-by":"crossref","unstructured":"Longley MJ, Lee J, Jung J, Lohoff FW. Epigenetics of alcohol use disorder\u2013a review of recent advances in DNA methylation profiling. Addict Biol. 2021;26:e13006.","DOI":"10.1111\/adb.13006"},{"key":"1378_CR17","doi-asserted-by":"crossref","unstructured":"Gatta E, Grayson DR, Auta J, Saudagar V, Dong E, Chen Y, et al. Genome-wide methylation in alcohol use disorder subjects: implications for an epigenetic regulation of the cortico-limbic glucocorticoid receptors (NR3C1). Mol Psychiatry. 2021;26:1029\u201341.","DOI":"10.1038\/s41380-019-0449-6"},{"key":"1378_CR18","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1093\/ije\/dys084","volume":"42","author":"BH Smith","year":"2013","unstructured":"Smith BH, Campbell A, Linksted P, Fitzpatrick B, Jackson C, Kerr SM, et al. Cohort profile: Generation Scotland: Scottish Family Health Study (GS:SFHS). The study, its participants and their potential for genetic research on health and illness. Int J Epidemiol. 2013;42:689\u2013700.","journal-title":"Int J Epidemiol"},{"key":"1378_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-7-74","volume":"7","author":"BH Smith","year":"2006","unstructured":"Smith BH, Campbell H, Blackwood D, Connell J, Connor M, Deary IJ, et al. Generation Scotland: the Scottish Family Health Study; a new resource for researching genes and heritability. BMC Med Genet. 2006;7:74.","journal-title":"BMC Med Genet"},{"key":"1378_CR20","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1038\/mp.2017.153","volume":"22","author":"TK Clarke","year":"2017","unstructured":"Clarke TK, Adams MJ, Davies G, Howard DM, Hall LS, Padmanabhan S, et al. Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N\u2009=\u2009112 117). Mol Psychiatry. 2017;22:1376\u201384.","journal-title":"Mol Psychiatry"},{"key":"1378_CR21","unstructured":"First MB. Structured clinical interview for DSM-IV Axis I Disorders. Biometrics Research Department, 1997."},{"key":"1378_CR22","doi-asserted-by":"publisher","first-page":"378","DOI":"10.15288\/jsad.2015.76.378","volume":"76","author":"RB Goldstein","year":"2015","unstructured":"Goldstein RB, Chou SP, Smith SM, Jung J, Zhang H, Saha TD, et al. Nosologic comparisons of DSM-IV and DSM-5 alcohol and drug use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. J Stud Alcohol Drugs. 2015;76:378\u201388.","journal-title":"J Stud Alcohol Drugs"},{"key":"1378_CR23","doi-asserted-by":"crossref","unstructured":"Muench C, Charlet K, Balderston NL, Grillon C, Heilig M, Cortes CR, et al. Fear conditioning and extinction in alcohol dependence: evidence for abnormal amygdala reactivity. Addict Biol. 2021;26:e12835.","DOI":"10.1111\/adb.12835"},{"key":"1378_CR24","doi-asserted-by":"publisher","first-page":"175","DOI":"10.12688\/f1000research.4680.2","volume":"3","author":"JP Fortin","year":"2014","unstructured":"Fortin JP, Fertig E, Hansen K. shinyMethyl: interactive quality control of Illumina 450k DNA methylation arrays in R. F1000Res. 2014;3:175.","journal-title":"F1000Res"},{"key":"1378_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-293","volume":"14","author":"R Pidsley","year":"2013","unstructured":"Pidsley R, CC YW, Volta M, Lunnon K, Mill J, Schalkwyk LC. A data-driven approach to preprocessing Illumina 450K methylation array data. BMC Genomics. 2013;14:293.","journal-title":"BMC Genomics"},{"key":"1378_CR26","doi-asserted-by":"publisher","first-page":"5112","DOI":"10.1038\/s41380-020-0808-3","volume":"26","author":"MC Barbu","year":"2021","unstructured":"Barbu MC, Shen X, Walker RM, Howard DM, Evans KL, Whalley HC, et al. Epigenetic prediction of major depressive disorder. Mol Psychiatry. 2021;26:5112\u201323.","journal-title":"Mol Psychiatry"},{"key":"1378_CR27","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","volume":"26","author":"CJ Willer","year":"2010","unstructured":"Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26:2190\u20131.","journal-title":"Bioinformatics"},{"key":"1378_CR28","doi-asserted-by":"crossref","unstructured":"Suderman M, Staley JR, French R, Arathimos R, Simpkin A, Tilling K. dmrff: identifying differentially methylated regions efficiently with power and control. bioRxiv [Preprint]. 2018:508556.","DOI":"10.1101\/508556"},{"key":"1378_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5","volume":"8","author":"K Watanabe","year":"2017","unstructured":"Watanabe K, Taskesen E, van Bochoven A, Posthuma D. Functional mapping and annotation of genetic associations with FUMA. Nat Commun. 2017;8:1826.","journal-title":"Nat Commun"},{"key":"1378_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11181-1","volume":"10","author":"K Watanabe","year":"2019","unstructured":"Watanabe K, Umi\u0107evi\u0107 Mirkov M, de Leeuw CA, van den Heuvel MP, Posthuma D. Genetic mapping of cell type specificity for complex traits. Nat Commun. 2019;10:3222.","journal-title":"Nat Commun"},{"key":"1378_CR31","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1038\/s41593-018-0275-1","volume":"21","author":"RK Walters","year":"2018","unstructured":"Walters RK, Polimanti R, Johnson EC, McClintick JN, Adams MJ, Adkins AE, et al. Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. Nat Neurosci. 2018;21:1656\u201369.","journal-title":"Nat Neurosci"},{"key":"1378_CR32","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, Li Y, Brazel DM, Chen F, 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;51:237\u201344.","journal-title":"Nat Genet"},{"key":"1378_CR33","doi-asserted-by":"crossref","unstructured":"Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.","DOI":"10.7554\/eLife.34408"},{"key":"1378_CR34","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1002\/sim.7221","volume":"36","author":"J Bowden","year":"2017","unstructured":"Bowden J, Del Greco MF, Minelli C, Smith GD, Sheehan N, Thompson J. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med. 2017;36:1783\u2013802.","journal-title":"Stat Med"},{"key":"1378_CR35","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1093\/ije\/dyy258","volume":"48","author":"J Bowden","year":"2019","unstructured":"Bowden J, Del Greco MF, Minelli C, Zhao Q, Lawlor DA, Sheehan NA, et al. Improving the accuracy of two-sample summary-data Mendelian randomization: moving beyond the NOME assumption. Int J Epidemiol. 2019;48:728\u201342.","journal-title":"Int J Epidemiol"},{"key":"1378_CR36","doi-asserted-by":"publisher","first-page":"e1007081","DOI":"10.1371\/journal.pgen.1007081","volume":"13","author":"G Hemani","year":"2017","unstructured":"Hemani G, Tilling K, Davey, Smith G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLOS Genet. 2017;13:e1007081.","journal-title":"PLOS Genet"},{"key":"1378_CR37","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;50:693\u20138.","journal-title":"Nat Genet"},{"key":"1378_CR38","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/gepi.21998","volume":"40","author":"S Burgess","year":"2016","unstructured":"Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol. 2016;40:597\u2013608.","journal-title":"Genet Epidemiol"},{"key":"1378_CR39","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41386-019-0500-y","volume":"45","author":"A Luo","year":"2020","unstructured":"Luo A, Jung J, Longley M, Rosoff DB, Charlet K, Muench C, et al. Epigenetic aging is accelerated in alcohol use disorder and regulated by genetic variation in APOL2. Neuropsychopharmacology. 2020;45:327\u201336.","journal-title":"Neuropsychopharmacology"},{"key":"1378_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53603-6","volume":"9","author":"JS Lee","year":"2019","unstructured":"Lee JS, Mukhopadhyay P, Matyas C, Trojnar E, Paloczi J, Yang YR, et al. PCSK9 inhibition as a novel therapeutic target for alcoholic liver disease. Sci Rep. 2019;9:17167.","journal-title":"Sci Rep"},{"key":"1378_CR41","doi-asserted-by":"publisher","first-page":"7394","DOI":"10.1128\/MCB.01087-08","volume":"28","author":"AM Pilon","year":"2008","unstructured":"Pilon AM, Arcasoy MO, Dressman HK, Vayda SE, Maksimova YD, Sangerman JI, et al. Failure of terminal erythroid differentiation in EKLF-deficient mice is associated with cell cycle perturbation and reduced expression of E2F2. Mol Cell Biol. 2008;28:7394\u2013401.","journal-title":"Mol Cell Biol"},{"key":"1378_CR42","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1073\/pnas.0308512100","volume":"101","author":"EM Blalock","year":"2004","unstructured":"Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW. Incipient Alzheimer\u2019s disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci USA. 2004;101:2173\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1378_CR43","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, Pfeiffer L, Tsai PC, Reynolds LM, et al. A DNA methylation biomarker of alcohol consumption. Mol Psychiatry. 2018;23:422\u201333.","journal-title":"Mol Psychiatry"},{"key":"1378_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1063-4","volume":"17","author":"J Bohlin","year":"2016","unstructured":"Bohlin J, H\u00e5berg SE, Magnus P, Reese SE, Gjessing HK, Magnus MC, et al. Prediction of gestational age based on genome-wide differentially methylated regions. Genome Biol. 2016;17:207.","journal-title":"Genome Biol"},{"key":"1378_CR45","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-860","volume":"15","author":"MJ Bonder","year":"2014","unstructured":"Bonder MJ, Kasela S, Kals M, Tamm R, Lokk K, Barragan I, et al. Genetic and epigenetic regulation of gene expression in fetal and adult human livers. BMC Genomics. 2014;15:860.","journal-title":"BMC Genomics"},{"key":"1378_CR46","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1381-z","volume":"16","author":"S Marttila","year":"2015","unstructured":"Marttila S, Kananen L, H\u00e4yrynen S, Jylh\u00e4v\u00e4 J, Nevalainen T, Hervonen A, et al. Ageing-associated changes in the human DNA methylome: genomic locations and effects on gene expression. BMC Genomics. 2015;16:179.","journal-title":"BMC Genomics"},{"key":"1378_CR47","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1101\/gr.180273.114","volume":"25","author":"H Spiers","year":"2015","unstructured":"Spiers H, Hannon E, Schalkwyk LC, Smith R, Wong CCY, O\u2019Donovan MC, et al. Methylomic trajectories across human fetal brain development. Genome Res. 2015;25:338\u201352.","journal-title":"Genome Res"},{"key":"1378_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-016-3452-1","volume":"18","author":"CJ Xu","year":"2017","unstructured":"Xu CJ, Bonder MJ, S\u00f6derh\u00e4ll C, Bustamante M, Ba\u00efz N, Gehring U, et al. The emerging landscape of dynamic DNA methylation in early childhood. BMC Genomics. 2017;18:25.","journal-title":"BMC Genomics"},{"key":"1378_CR49","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1002\/ajmg.b.32565","volume":"174","author":"MV Dogan","year":"2017","unstructured":"Dogan MV, Beach SRH, Philibert RA. Genetically contextual effects of smoking on genome wide DNA methylation. Am J Med Genet Part B Neuropsychiatr Genet. 2017;174:595\u2013607.","journal-title":"Am J Med Genet Part B Neuropsychiatr Genet"},{"key":"1378_CR50","doi-asserted-by":"publisher","first-page":"e63812","DOI":"10.1371\/journal.pone.0063812","volume":"8","author":"S Zeilinger","year":"2013","unstructured":"Zeilinger S, K\u00fchnel B, Klopp N, Baurecht H, Kleinschmidt A, Gieger C, et al. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PloS One. 2013;8:e63812.","journal-title":"PloS One"},{"key":"1378_CR51","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.ajhg.2016.02.019","volume":"98","author":"BR Joubert","year":"2016","unstructured":"Joubert BR, Felix JF, Yousefi P, Bakulski KM, Just AC, Breton C, et al. DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis. Am J Hum Genet. 2016;98:680\u201396.","journal-title":"Am J Hum Genet"},{"key":"1378_CR52","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1002\/ijc.28765","volume":"135","author":"K Nones","year":"2014","unstructured":"Nones K, Waddell N, Song S, Patch AM, Miller D, Johns A, et al. Genome-wide DNA methylation patterns in pancreatic ductal adenocarcinoma reveal epigenetic deregulation of SLIT-ROBO, ITGA2 and MET signaling. Int J Cancer. 2014;135:1110\u20138.","journal-title":"Int J Cancer"},{"key":"1378_CR53","doi-asserted-by":"publisher","first-page":"e57886","DOI":"10.1371\/journal.pone.0057886","volume":"8","author":"MB Wozniak","year":"2013","unstructured":"Wozniak MB, Le Calvez-Kelm F, Abedi-Ardekani B, Byrnes G, Durand G, Carreira C, et al. Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States. PloS One. 2013;8:e57886.","journal-title":"PloS One"},{"key":"1378_CR54","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1136\/annrheumdis-2015-208659","volume":"75","author":"J Imgenberg-Kreuz","year":"2016","unstructured":"Imgenberg-Kreuz J, Sandling JK, Alml\u00f6f JC, Nordlund J, Sign\u00e9r L, Norheim KB, et al. Genome-wide DNA methylation analysis in multiple tissues in primary Sj\u00f6gren\u2019s syndrome reveals regulatory effects at interferon-induced genes. Ann Rheum Dis. 2016;75:2029\u201336.","journal-title":"Ann Rheum Dis"},{"key":"1378_CR55","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/nbt.2487","volume":"31","author":"Y Liu","year":"2013","unstructured":"Liu Y, Aryee MJ, Padyukov L, Fallin MD, Hesselberg E, Runarsson A, et al. Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis. Nat Biotechnol. 2013;31:142\u20137.","journal-title":"Nat Biotechnol"},{"key":"1378_CR56","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-016-0304-4","volume":"9","author":"KVE Braun","year":"2017","unstructured":"Braun KVE, Dhana K, de Vries PS, Voortman T, van Meurs JBJ, Uitterlinden AG, et al. Epigenome-wide association study (EWAS) on lipids: the Rotterdam Study. Clin Epigenetics. 2017;9:15.","journal-title":"Clin Epigenetics"},{"key":"1378_CR57","doi-asserted-by":"publisher","DOI":"10.1186\/s12919-018-0119-8","volume":"12","author":"S Sayols-Baixeras","year":"2018","unstructured":"Sayols-Baixeras S, Tiwari HK, Aslibekyan SW. Disentangling associations between DNA methylation and blood lipids: a Mendelian randomization approach. BMC Proc. 2018;12:23.","journal-title":"BMC Proc"},{"key":"1378_CR58","doi-asserted-by":"publisher","first-page":"e001487","DOI":"10.1161\/CIRCGENETICS.116.001487","volume":"10","author":"\u00c5K Hedman","year":"2017","unstructured":"Hedman \u00c5K, Mendelson MM, Marioni RE, Gustafsson S, Joehanes R, Irvin MR, et al. Epigenetic patterns in blood associated with lipid traits predict incident coronary heart disease events and are enriched for results from genome-wide association studies. Circ Cardiovasc Genet. 2017;10:e001487.","journal-title":"Circ Cardiovasc Genet"},{"key":"1378_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","volume":"32","author":"GD Smith","year":"2003","unstructured":"Smith GD, Ebrahim S. \u2018Mendelian randomization\u2019: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1\u201322.","journal-title":"Int J Epidemiol"},{"key":"1378_CR60","doi-asserted-by":"publisher","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","volume":"23","author":"G Davey Smith","year":"2014","unstructured":"Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23:R89\u201398.","journal-title":"Hum Mol Genet"},{"key":"1378_CR61","doi-asserted-by":"publisher","first-page":"e1003410","DOI":"10.1371\/journal.pmed.1003410","volume":"17","author":"DB Rosoff","year":"2020","unstructured":"Rosoff DB, Davey Smith G, Mehta N, Clarke TK, Lohoff FW. Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: a multivariable Mendelian randomization study. PLoS Med. 2020;17:e1003410.","journal-title":"PLoS Med"},{"key":"1378_CR62","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1001\/jamapsychiatry.2020.3554","volume":"78","author":"DB Rosoff","year":"2021","unstructured":"Rosoff DB, Smith GD, Lohoff FW. Prescription opioid use and risk for major depressive disorder and anxiety and stress-related disorders: a multivariable Mendelian randomization analysis. JAMA psychiatry. 2021;78:151\u201360.","journal-title":"JAMA psychiatry"},{"key":"1378_CR63","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1038\/s41380-019-0535-9","volume":"26","author":"DB Rosoff","year":"2021","unstructured":"Rosoff DB, Clarke TK, Adams MJ, McIntosh AM, Davey Smith G, Jung J, et al. Educational attainment impacts drinking behaviors and risk for alcohol dependence: results from a two-sample Mendelian randomization study with ~780,000 participants. Mol Psychiatry. 2021;26:1119\u201332.","journal-title":"Mol Psychiatry"},{"key":"1378_CR64","doi-asserted-by":"crossref","unstructured":"Dugu\u00e9 P-A, Wilson R, Lehne B, Jayasekara H, Wang X, Jung C-H, et al. Alcohol consumption is associated with widespread changes in blood DNA methylation: analysis of cross-sectional and longitudinal data. Addict Biol. 2021;26:e12855.","DOI":"10.1111\/adb.12855"},{"key":"1378_CR65","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1053\/j.gastro.2017.06.003","volume":"153","author":"J Nano","year":"2017","unstructured":"Nano J, Ghanbari M, Wang W, de Vries PS, Dhana K, Muka T, et al. Epigenome-wide association study identifies methylation sites associated with liver enzymes and hepatic steatosis. Gastroenterology. 2017;153:1096\u2013e1092.","journal-title":"Gastroenterology"},{"key":"1378_CR66","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1111\/j.1476-5381.2011.01480.x","volume":"165","author":"RJ Bridges","year":"2012","unstructured":"Bridges RJ, Natale NR, Patel SA. System xc\u2212 cystine\/glutamate antiporter: an update on molecular pharmacology and roles within the CNS. Br J Pharmacol. 2012;165:20\u201334.","journal-title":"Br J Pharmacol"},{"key":"1378_CR67","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1089\/ars.2000.2.4-665","volume":"2","author":"H Sato","year":"2000","unstructured":"Sato H, Tamba M, Kuriyama-Matsumura K, Okuno S, Bannai S. Molecular cloning and expression of human xCT, the light chain of amino acid transport system xc\u2212. Antioxid Redox Signal. 2000;2:665\u201371.","journal-title":"Antioxid Redox Signal"},{"key":"1378_CR68","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/0304-4157(84)90014-5","volume":"779","author":"S Bannai","year":"1984","unstructured":"Bannai S. Transport of cystine and cysteine in mammalian cells. Biochim Biophys Acta. 1984;779:289\u2013306.","journal-title":"Biochim Biophys Acta"},{"key":"1378_CR69","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1016\/S0021-9258(17)35926-4","volume":"261","author":"S Bannai","year":"1986","unstructured":"Bannai S. Exchange of cystine and glutamate across plasma membrane of human fibroblasts. J Biol Chem. 1986;261:2256\u201363.","journal-title":"J Biol Chem"},{"key":"1378_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15065-7","volume":"11","author":"CL Vallerga","year":"2020","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;11:1238.","journal-title":"Nat Commun"},{"key":"1378_CR71","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/j.cmet.2019.08.001","volume":"30","author":"WM Choi","year":"2019","unstructured":"Choi WM, Kim HH, Kim MH, Cinar R, Yi HS, Eun HS, et al. Glutamate signaling in hepatic stellate cells drives alcoholic steatosis. Cell Metab. 2019;30:877\u201389.e877.","journal-title":"Cell Metab"},{"key":"1378_CR72","doi-asserted-by":"crossref","unstructured":"Peana AT, Muggironi G, Bennardini F. Change of cystine\/glutamate antiporter expression in ethanol-dependent rats. Front Neurosci. 2014;8:311.","DOI":"10.3389\/fnins.2014.00311"},{"key":"1378_CR73","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.2337\/db18-1193","volume":"68","author":"J Ma","year":"2019","unstructured":"Ma J, Nano J, Ding J, Zheng Y, Hennein R, Liu C, et al. A peripheral blood DNA methylation signature of hepatic fat reveals a potential causal pathway for nonalcoholic fatty liver disease. Diabetes. 2019;68:1073\u201383.","journal-title":"Diabetes"},{"key":"1378_CR74","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s13238-020-00789-5","volume":"12","author":"P Koppula","year":"2021","unstructured":"Koppula P, Zhuang L, Gan B. Cystine transporter SLC7A11\/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy. Protein Cell. 2021;12:599\u2013620.","journal-title":"Protein Cell"},{"key":"1378_CR75","first-page":"3106","volume":"10","author":"W Lin","year":"2020","unstructured":"Lin W, Wang C, Liu G, Bi C, Wang X, Zhou Q, et al. SLC7A11\/xCT in cancer: biological functions and therapeutic implications. Am J Cancer Res. 2020;10:3106\u201326.","journal-title":"Am J Cancer Res"},{"key":"1378_CR76","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.neubiorev.2015.04.015","volume":"55","author":"J Deepmala, Slattery","year":"2015","unstructured":"Deepmala, Slattery J, Kumar N, Delhey L, Berk M, Dean O. Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic review. Neurosci Biobehav Rev. 2015;55:294\u2013321.","journal-title":"Neurosci Biobehav Rev"},{"key":"1378_CR77","doi-asserted-by":"publisher","first-page":"2469486","DOI":"10.1155\/2018\/2469486","volume":"2018","author":"SL Ooi","year":"2018","unstructured":"Ooi SL, Green R, Pak SC. N-acetylcysteine for the treatment of psychiatric disorders: a review of current evidence. Biomed Res Int. 2018;2018:2469486.","journal-title":"Biomed Res Int"},{"key":"1378_CR78","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1111\/bph.15456","volume":"178","author":"I Smaga","year":"2021","unstructured":"Smaga I, Frankowska M, Filip M. N-acetylcysteine as a new prominent approach for treating psychiatric disorders. Br J Pharm. 2021;178:2569\u201394.","journal-title":"Br J Pharm"},{"key":"1378_CR79","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1016\/j.ajhg.2017.09.028","volume":"101","author":"MA Richard","year":"2017","unstructured":"Richard MA, Huan T, Ligthart S, Gondalia R, Jhun MA, Brody JA, et al. DNA methylation analysis identifies loci for blood pressure regulation. Am J Hum Genet. 2017;101:888\u2013902.","journal-title":"Am J Hum Genet"},{"key":"1378_CR80","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1161\/01.HYP.9.2.111","volume":"9","author":"S MacMahon","year":"1987","unstructured":"MacMahon S. Alcohol consumption and hypertension. Hypertension. 1987;9:111\u201321.","journal-title":"Hypertension"},{"key":"1378_CR81","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1097\/01.hjh.0000239283.35562.15","volume":"24","author":"G Soardo","year":"2006","unstructured":"Soardo G, Donnini D, Varutti R, Milocco C, Basan L, Esposito W, et al. Effects of alcohol withdrawal on blood pressure in hypertensive heavy drinkers. J Hypertens. 2006;24:1493\u20138.","journal-title":"J Hypertens"},{"key":"1378_CR82","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/alcalc\/agh221","volume":"41","author":"M Ceccanti","year":"2006","unstructured":"Ceccanti M, Sasso GF, Nocente R, Balducci G, Prastaro A, Ticchi C, et al. Hypertension in early alcohol withdrawal in chronic alcoholics. Alcohol Alcohol. 2006;41:5\u201310.","journal-title":"Alcohol Alcohol"},{"key":"1378_CR83","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1016\/S2468-2667(17)30003-8","volume":"2","author":"M Roerecke","year":"2017","unstructured":"Roerecke M, Kaczorowski J, Tobe SW, Gmel G, Hasan OSM, Rehm J. The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis. Lancet Public Health. 2017;2:e108\u2013e120.","journal-title":"Lancet Public Health"},{"key":"1378_CR84","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-54","volume":"9","author":"K Bitton-Worms","year":"2010","unstructured":"Bitton-Worms K, Pikarsky E, Aronheim A. The AP-1 repressor protein, JDP2, potentiates hepatocellular carcinoma in mice. Mol Cancer. 2010;9:54.","journal-title":"Mol Cancer"},{"key":"1378_CR85","doi-asserted-by":"publisher","first-page":"3206","DOI":"10.1021\/bi992211q","volume":"39","author":"KL Jordan-Sciutto","year":"2000","unstructured":"Jordan-Sciutto KL, Dragich JM, Caltagarone J, Hall DJ, Bowser R. Fetal Alz-50 clone 1 (FAC1) protein interacts with the Myc-associated zinc finger protein (ZF87\/MAZ) and alters its transcriptional activity. Biochemistry. 2000;39:3206\u201315.","journal-title":"Biochemistry"},{"key":"1378_CR86","doi-asserted-by":"publisher","first-page":"87","DOI":"10.2147\/NDT.S198772","volume":"16","author":"C Wiegmann","year":"2020","unstructured":"Wiegmann C, Mick I, Brandl EJ, Heinz A, Gutwinski S. Alcohol and dementia \u2013 what is the link? A systematic review. Neuropsychiatr Dis Treat. 2020;16:87\u201399.","journal-title":"Neuropsychiatr Dis Treat"},{"key":"1378_CR87","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s10654-017-0225-3","volume":"32","author":"W Xu","year":"2017","unstructured":"Xu W, Wang H, Wan Y, Tan C, Li J, Tan L, et al. Alcohol consumption and dementia risk: a dose-response meta-analysis of prospective studies. Eur J Epidemiol. 2017;32:31\u201342.","journal-title":"Eur J Epidemiol"},{"key":"1378_CR88","first-page":"26","volume":"8","author":"HR Tavakoli","year":"2011","unstructured":"Tavakoli HR, Hull M, Michael Okasinski L. Review of current clinical biomarkers for the detection of alcohol dependence. Innov Clin Neurosci. 2011;8:26\u201333.","journal-title":"Innov Clin Neurosci"},{"key":"1378_CR89","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1111\/acer.13373","volume":"41","author":"AC Justice","year":"2017","unstructured":"Justice AC, McGinnis KA, Tate JP, Xu K, Becker WC, Zhao H, et al. Validating harmful alcohol use as a phenotype for genetic discovery using phosphatidylethanol and a polymorphism in ADH1B. Alcohol Clin Exp Res. 2017;41:998\u20131003.","journal-title":"Alcohol Clin Exp Res"},{"key":"1378_CR90","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s00414-016-1445-x","volume":"131","author":"A Schrock","year":"2017","unstructured":"Schrock A, Thierauf-Emberger A, Schurch S, Weinmann W. Phosphatidylethanol (PEth) detected in blood for 3 to 12 days after single consumption of alcohol\u2013a drinking study with 16 volunteers. Int J Leg Med. 2017;131:153\u201360.","journal-title":"Int J Leg Med"},{"key":"1378_CR91","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1111\/acer.13213","volume":"40","author":"JA Hahn","year":"2016","unstructured":"Hahn JA, Anton RF, Javors MA. The formation, elimination, interpretation, and future research needs of phosphatidylethanol for research studies and clinical practice. Alcohol Clin Exp Res. 2016;40:2292\u20135.","journal-title":"Alcohol Clin Exp Res"},{"key":"1378_CR92","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1514-1","volume":"19","author":"DL McCartney","year":"2018","unstructured":"McCartney DL, Hillary RF, Stevenson AJ, Ritchie SJ, Walker RM, Zhang Q, et al. Epigenetic prediction of complex traits and death. Genome Biol. 2018;19:136.","journal-title":"Genome Biol"},{"key":"1378_CR93","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-019-0753-7","volume":"11","author":"PD Yousefi","year":"2019","unstructured":"Yousefi PD, Richmond R, Langdon R, Ness A, Liu C, Levy D, et al. Validation and characterisation of a DNA methylation alcohol biomarker across the life course. Clin Epigenetics. 2019;11:163.","journal-title":"Clin Epigenetics"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01378-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01378-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01378-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T03:40:52Z","timestamp":1652326852000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-021-01378-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":93,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["1378"],"URL":"https:\/\/doi.org\/10.1038\/s41380-021-01378-6","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]},"assertion":[{"value":"15 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"AMM has received grant support from Pfizer, Eli Lilly, Janssen, and The Sackler Trust. These sources are not connected to the current investigation. AMM has also received speaker fees from Janssen and Illumina. The remaining authors report no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Ethics approval for Generation Scotland was given by the NHS Tayside committee on research ethics (reference 15\/ES\/0040).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All participants provided written informed consent for the use of their data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}