{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T10:29:14Z","timestamp":1771669754965,"version":"3.50.1"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T00:00:00Z","timestamp":1555027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0215026","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T17:34:46Z","timestamp":1555090486000},"page":"e0215026","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["An exploratory phenome wide association study linking asthma and liver disease genetic variants to electronic health records from the Estonian Biobank"],"prefix":"10.1371","volume":"14","author":[{"given":"Glen","family":"James","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6835-9632","authenticated-orcid":true,"given":"Sulev","family":"Reisberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaido","family":"Lepik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Galwey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Avillach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liis","family":"Kolberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reedik","family":"M\u00e4gi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T\u00f5nu","family":"Esko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myriam","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn","family":"Waterworth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Katrina","family":"Loomis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaak","family":"Vilo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2019,4,12]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/ng.3314","article-title":"The support of human genetic evidence for approved drug indications","volume":"47","author":"MR Nelson","year":"2015","journal-title":"Nat Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"9362","DOI":"10.1073\/pnas.0903103106","article-title":"Potential etiologic and functional implications of genome-wide association loci for human diseases and traits","volume":"106","author":"LA Hindorff","year":"2009","journal-title":"Proc Natl Acad Sci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/imm.12195","article-title":"The challenges, advantages and future of phenome-wide association studies","author":"SJ Hebbring","year":"2014","journal-title":"Immunology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.12688\/wellcomeopenres.12600.1","article-title":"Electronic health record and genome-wide genetic data in Generation Scotland participants","volume":"2","author":"SM Kerr","year":"2017","journal-title":"Wellcome Open Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1093\/ije\/dyt268","article-title":"Cohort profile: Estonian biobank of the Estonian genome center, university of Tartu","volume":"44","author":"L Leitsalu","year":"2015","journal-title":"Int J Epidemiol"},{"key":"ref6","year":"2017"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/nrgastro.2013.182","article-title":"The genetics of NAFLD.","author":"QM Anstee","year":"2013","journal-title":"Nature Reviews Gastroenterology and Hepatology"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/ng.488","article-title":"Variant in PNPLA3 is associated with alcoholic liver disease","volume":"42","author":"C Tian","year":"2010","journal-title":"Nat Genet"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1002\/hep.23832","article-title":"A common variant in the patatin-like phospholipase 3 gene (PNPLA3) is associated with fatty liver disease in obese children and adolescents","volume":"52","author":"N Santoro","year":"2010","journal-title":"Hepatology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.2174\/13816128113199990381","article-title":"Genetic predisposition in NAFLD and NASH: impact on severity of liver disease and response to treatment","volume":"19","author":"P Dongiovanni","year":"2013","journal-title":"Curr Pharm Des"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/ng.257","article-title":"Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease","volume":"40","author":"S Romeo","year":"2008","journal-title":"Nat Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/hep.28370","article-title":"The rs2294918 E434K variant modulates patatin-like phospholipase domain-containing 3 expression and liver damage","volume":"63","author":"B Donati","year":"2016","journal-title":"Hepatology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/ng.2901","article-title":"Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease","volume":"46","author":"J Kozlitina","year":"2014","journal-title":"Nat Genet"},{"key":"ref14","first-page":"1","article-title":"Relationships between Genetic Variations of PNPLA3, TM6SF2 and Histological Features of Nonalcoholic Fatty Liver Disease in Japan","volume":"10","author":"N Akuta","year":"2015","journal-title":"Gut Liver"},{"key":"ref15","first-page":"5","article-title":"TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease","author":"Y-L Liu","year":"2014","journal-title":"Nat Commun"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jhep.2011.05.029","article-title":"The SOD2 C47T polymorphism influences NAFLD fibrosis severity: Evidence from case-control and intra-familial allele association studies","volume":"56","author":"A Al-Serri","year":"2012","journal-title":"J Hepatol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.4254\/wjh.v9.i26.1101","article-title":"Regional differences in genetic susceptibility to nonalcoholic liver disease in two distinct Indian ethnicities","volume":"9","author":"G Bale","year":"2017","journal-title":"World J Hepatol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1002\/hep.27695","article-title":"Altered hepatic gene expression in nonalcoholic fatty liver disease is associated with lower hepatic n-3 and n-6 polyunsaturated fatty acids","volume":"61","author":"BM Arendt","year":"2015","journal-title":"Hepatology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"623e8","DOI":"10.1053\/j.gastro.2015.05.039","article-title":"High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery","volume":"149","author":"SA Xanthakos","year":"2015","journal-title":"Gastroenterology"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"827","DOI":"10.4254\/wjh.v8.i20.827","article-title":"Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management","volume":"8","author":"VV Ravi Kanth","year":"2016","journal-title":"World J Hepatol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.ajhg.2008.09.012","article-title":"Population-Based Genome-wide Association Studies Reveal Six Loci Influencing Plasma Levels of Liver Enzymes","volume":"83","author":"X Yuan","year":"2008","journal-title":"Am J Hum Genet"},{"key":"ref22","article-title":"A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease","author":"NS Abul-Husn","year":"2018","journal-title":"N Engl J Med"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1056\/NEJMoa0907295","article-title":"Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease","volume":"362","author":"KF Petersen","year":"2010","journal-title":"N Engl J Med"},{"key":"ref24","doi-asserted-by":"crossref","DOI":"10.1507\/endocrj.EJ14-0052","article-title":"Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits","volume":"61","author":"A Kitamoto","year":"2014","journal-title":"Endocr J"},{"key":"ref25","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1001324","article-title":"Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits","volume":"7","author":"EK Speliotes","year":"2011","journal-title":"PLoS Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s11033-010-0212-1","article-title":"Genetic variation in the GCKR gene is associated with non-alcoholic fatty liver disease in Chinese people","volume":"38","author":"Z Yang","year":"2011","journal-title":"Mol Biol Rep"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00592-015-0766-4","article-title":"GCKR polymorphism influences liver fat content in patients with type 2 diabetes.","volume":"53","author":"J-M Petit","year":"2016","journal-title":"Acta Diabetol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1053\/j.gastro.2016.01.032","article-title":"The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent","volume":"150","author":"RM Mancina","year":"2016","journal-title":"Gastroenterology"},{"key":"ref29","first-page":"143","article-title":"Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection","author":"E Patin","year":"2012","journal-title":"Gastroenterology"},{"key":"ref30","unstructured":"World Health Organization. Asthma Fact Sheet [Internet]. 2016 [cited 20 Sep 2018]. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/asthma\" xlink:type=\"simple\">http:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/asthma<\/ext-link>"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa0906312","article-title":"A large-scale, consortium-based genomewide association study of asthma","volume":"363","author":"MF Moffatt","year":"2010","journal-title":"N Engl J Med"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1080\/02770903.2016.1196371","article-title":"BIRC3 single nucleotide polymorphism associate with asthma susceptibility and the abundance of eosinophils and neutrophils","volume":"54","author":"E Roscioli","year":"2017","journal-title":"J Asthma"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.cell.2016.10.042","article-title":"The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease","volume":"167","author":"WJ Astle","year":"2016","journal-title":"Cell"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.jhep.2015.10.016","article-title":"MERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease","volume":"64","author":"S Petta","year":"2016","journal-title":"J Hepatol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.jaci.2010.06.030","article-title":"Analyses of shared genetic factors between asthma and obesity in children","volume":"126","author":"E Mel\u00e9n","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"ref36","article-title":"Inflammation, stress, and diabetes","author":"K. E. Wellen","year":"2005","journal-title":"Journal of Clinical Investigation"},{"key":"ref37","article-title":"Systematic review of genetic association studies involving histologically confirmed non-Alcoholic fatty liver disease","author":"KL Wood","year":"2015","journal-title":"BMJ Open Gastroenterology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/MOG.0000000000000175","article-title":"Nonalcoholic fatty liver disease: New treatments.","author":"T Hardy","year":"2015","journal-title":"Current Opinion in Gastroenterology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1093\/bioinformatics\/btn564","article-title":"SNAP: A web-based tool for identification and annotation of proxy SNPs using HapMap","volume":"24","author":"AD Johnson","year":"2008","journal-title":"Bioinformatics"},{"key":"ref40","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1003405","article-title":"Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics.","volume":"9","author":"A Neuraz","year":"2013","journal-title":"PLoS Comput Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses","volume":"81","author":"S Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1093\/bioinformatics\/btq126","article-title":"PheWAS: Demonstrating the feasibility of a phenome-wide scan to discover gene-disease associations","volume":"26","author":"JC Denny","year":"2010","journal-title":"Bioinformatics"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/ng.970","article-title":"Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma","volume":"43","author":"JC Chambers","year":"2011","journal-title":"Nat Genet"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.ajhg.2018.02.017","article-title":"PheWAS and Beyond: The Landscape of Associations with Medical Diagnoses and Clinical Measures across 38,662 Individuals from Geisinger","volume":"102","author":"A Verma","year":"2018","journal-title":"Am J Hum Genet"},{"key":"ref45","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0160573","article-title":"Phenome-Wide association study to explore relationships between immune system related genetic loci and complex traits and diseases","volume":"11","author":"A Verma","year":"2016","journal-title":"PLoS One"},{"key":"ref46","article-title":"Detection of Pleiotropy through a Phenome-Wide Association Study (PheWAS) of Epidemiologic Data as Part of the Environmental Architecture for Genes Linked to Environment (EAGLE) Study","volume":"10","author":"MA Hall","year":"2014","journal-title":"PLoS Genet"},{"key":"ref47","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003087","article-title":"Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network","volume":"9","author":"SA Pendergrass","year":"2013","journal-title":"PLoS Genet"},{"key":"ref48","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2014.00401","article-title":"Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eosinophilic Esophagitis","volume":"5","author":"B Namjou","year":"2014","journal-title":"Front Genet"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/art.39851","article-title":"Phenome-Wide Association Study of Rheumatoid Arthritis Subgroups Identifies Association Between Seronegative Disease and Fibromyalgia","volume":"69","author":"J Doss","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/gene.2013.2","article-title":"A PheWAS approach in studying HLA-DRB1*1501","volume":"14","author":"SJ Hebbring","year":"2013","journal-title":"Genes Immun"},{"key":"ref51","doi-asserted-by":"crossref","DOI":"10.1186\/s12920-016-0191-8","article-title":"EMERGE Phenome-Wide Association Study (PheWAS) identifies clinical associations and pleiotropy for stop-gain variants","volume":"9","author":"A Verma","year":"2016","journal-title":"BMC Med Genomics"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1093\/bioinformatics\/btv076","article-title":"Application of clinical text data for phenome-wide association studies (PheWASs).","volume":"31","author":"SJ Hebbring","year":"2015","journal-title":"Bioinformatics"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/hep.24072","article-title":"Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance","volume":"53","author":"J Kozlitina","year":"2011","journal-title":"Hepatology"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1034\/j.1399-0039.2002.600101.x","article-title":"Major histocompatibility complex class I-restricted antigen processing and presentation","author":"L. Van Kaer","year":"2002","journal-title":"Tissue Antigens"},{"key":"ref55","article-title":"Critical amino acid variations in HLA-DQB1* molecules confers susceptibility to Autoimmune Thyroid Disease in south India","volume":"1","author":"S Ramgopal","year":"2018","journal-title":"Genes Immun."},{"key":"ref56","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1055\/s-2004-825732","article-title":"HLA-DRB1*04 and HLA-DQB1*03 association with the atrophic but not with the goitrous form of chronic autoimmune thyroiditis in a Brazilian population","volume":"36","author":"D Engelbrecht Zantut-Wittmann","year":"2004","journal-title":"Horm Metab Res"},{"key":"ref57","first-page":"493","article-title":"HLA-DQB1*05 association with Hashimoto\u2019s thyroiditis in children of Northern Greek origin","volume":"45","author":"S Giza","year":"2008","journal-title":"Indian Pediatr"},{"key":"ref58","first-page":"878","article-title":"HLA-DQB1-associated susceptibility that distinguishes Hashimoto\u2019s thyroiditis from Graves\u2019 disease in type I diabetic patients","volume":"78","author":"P Santamaria","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"149","DOI":"10.4239\/wjd.v3.i8.149","article-title":"HLA-DQB1* alleles and genetic susceptibility to type 1 diabetes mellitus","volume":"3","author":"YM Mosaad","year":"2012","journal-title":"World J Diabetes"},{"key":"ref60","first-page":"1078","article-title":"Association between HLA-DQA1, -DQB1 gene polymorphisms and susceptibility to asthma in northern Chinese subjects","volume":"116","author":"J Gao","year":"2003","journal-title":"Chin Med J (Engl)."},{"key":"ref61","first-page":"215","article-title":"Association of HLA class II alleles with childhood asthma and total IgE levels","volume":"7","author":"M Movahedi","year":"2008","journal-title":"Iran J Allergy, Asthma Immunol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0215026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T17:33:53Z","timestamp":1589045633000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0215026"}},"subtitle":[],"editor":[{"given":"Gyaneshwer","family":"Chaubey","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2019,4,12]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0215026","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,12]]}}}