{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T14:33:44Z","timestamp":1769006024337,"version":"3.49.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T00:00:00Z","timestamp":1443398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0138677","type":"journal-article","created":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T17:44:16Z","timestamp":1443462256000},"page":"e0138677","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["A GWAS Study on Liver Function Test Using eMERGE Network Participants"],"prefix":"10.1371","volume":"10","author":[{"given":"Bahram","family":"Namjou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Marsolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Lingren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marylyn D.","family":"Ritchie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shefali S.","family":"Verma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth L.","family":"Cobb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra","family":"Perry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terrie E.","family":"Kitchner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murray H.","family":"Brilliant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peggy L.","family":"Peissig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth M.","family":"Borthwick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc S.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Grafton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail P.","family":"Jarvik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid A.","family":"Holm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John B.","family":"Harley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,9,28]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/clinchem\/47.1.81","article-title":"Evidence for a substantial genetic influence on biochemical liver function tests: results from a population-based Danish twin study","volume":"47","author":"L Bathum","year":"2001","journal-title":"Clin Chem"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1056\/NEJM199511023331802","article-title":"The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome","volume":"333","author":"PJ Bosma","year":"1995","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/00008571-199906000-00009","article-title":"UDPglucuronosyltransferase (UGT1A1*28 andUGT1A6*2) polymorphisms in Caucasians and Asians: Relationships to serum bilirubin concentrations","volume":"9","author":"JW Lampe","year":"1999","journal-title":"Pharmacogenetics"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/S1079-9796(03)00071-8","article-title":"The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): Hematologic and evolutionary implications","volume":"31","author":"A Premawardhena","year":"2003","journal-title":"Blood Cells Mol Dis"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1161\/CIRCULATIONAHA.106.633206","article-title":"Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart Study","volume":"114","author":"JP Lin","year":"2006","journal-title":"Circulation"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"12671","DOI":"10.1073\/pnas.231140698","article-title":"Mechanism of indinavir-induced hyperbilirubinemia","volume":"98","author":"SD Zucker","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1200\/JCO.2005.05.2464","article-title":"Irinogenetics: what is the right star?","volume":"24","author":"F Innocenti","year":"2006","journal-title":"J Clin Oncol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1006\/bbrc.1993.2610","article-title":"Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II","volume":"197","author":"S Aono","year":"1993","journal-title":"Biochem Biophys Res Commun"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1006\/bbrc.2002.6683","article-title":"Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia","volume":"292","author":"J Sugatani","year":"2002","journal-title":"Biochem Bio\u00acphys Res Commun"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1124\/dmd.31.1.108","article-title":"Glucuronidation of 7-ethyl-10-hydroxycamp\u00actothecin (SN-38), an active metabolite of irinotecan (CPT-11), by human UGT1A1 variants, G71R, P229Q, and Y486D","volume":"31","author":"H Jinno","year":"2003","journal-title":"Drug Metab Dispos"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1124\/mol.62.3.608","article-title":"Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hy\u00acdroxycamptothecin (SN-38)","volume":"62","author":"JF Gagn\u00e9","year":"2002","journal-title":"Mol Pharmacol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3349\/ymj.2014.55.1.232","article-title":"Comprehensive variant screening of the UGT gene family","volume":"55","author":"JY Kim","year":"2014","journal-title":"Yonsei Med J"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/humu.21133","article-title":"Crigler\u2013Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants","volume":"31","author":"N Sneitz","year":"2010","journal-title":"Hum Mutat"},{"key":"ref14","first-page":"150","article-title":"Molecular pathology of Crigler-Najjar type I and II and Gilbert\u2019s syndromes","volume":"84","author":"M Sampietro","year":"1999","journal-title":"Haematologica"},{"key":"ref15","first-page":"13","article-title":"The eMERGE Network: a consortium of biorepositories linked to electronic medical records data for conducting genomic studies. BMC Med","volume":"4","author":"CA McCarty","year":"2011","journal-title":"Genomics"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1093\/hmg\/ddp202","article-title":"Genome-wide association meta-analysis for total serum bilirubin levels","volume":"18","author":"AD Johnson","year":"2009","journal-title":"Hum Mol Genet"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"606","DOI":"10.4065\/mcp.2011.0178","article-title":"Mayo Genome Consortia: a genotype-phenotype resource for genome-wide association studies with an application to the analysis of circulating bilirubin levels","volume":"86","author":"SJ Bielinski","year":"2011","journal-title":"Mayo Clin Proc"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/gepi.21711","article-title":"A genome-wide association study for serum bilirubin levels and gene-environment interaction in a Chinese population","volume":"37","author":"X Dai","year":"2013","journal-title":"Genet Epidemiol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1093\/hmg\/ddq281","article-title":"Genome-wide association of serum bilirubin levels in Korean population","volume":"19","author":"TW Kang","year":"2010","journal-title":"Hum Mol Genet"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1093\/hmg\/ddp203","article-title":"common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia","volume":"18","author":"S Sanna","year":"2009","journal-title":"Hum Mol Genet"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/ejhg.2011.206","article-title":"UGT1A1 is a major locus influencing bilirubin levels in African Americans","volume":"20","author":"G Chen","year":"2012","journal-title":"Eur J Hum Genet"},{"key":"ref22","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":"ref23","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":"ref24","doi-asserted-by":"crossref","first-page":"679","DOI":"10.3851\/IMP2747","article-title":"Genome-wide association study to characterize serum bilirubin elevations in patients with HCV treated with GS-9256, an HCV NS3 serine protease inhibitor","volume":"19","author":"D Nelson","year":"2014","journal-title":"Antivir Ther"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3389\/fgene.2014.00370","article-title":"Imputation and quality control steps for combining multiple genome-wide datasets","volume":"5","author":"SS Verma","year":"2014","journal-title":"Front Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1534\/g3.111.001198","article-title":"Genotype imputation with thousands of genomes","volume":"1","author":"B Howie","year":"2011","journal-title":"G3 (Bethesda)"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/ng1847","article-title":"Principal components analysis corrects for stratification in genome-wide association studies","volume":"38","author":"AL Price","year":"2006","journal-title":"Nat Genet"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/clpt.2014.137","article-title":"Design and anticipated outcomes of the eMERGE-PGx project: a multicenter pilot for preemptive pharmacogenomics in electronic health record systems","volume":"96","author":"LJ Rasmussen-Torvik","year":"2014","journal-title":"Clin Pharmacol Ther"},{"key":"ref29","article-title":"Cecil Medicine","author":"PD Berk","year":"2011"},{"key":"ref30","article-title":"Sleisenger and Fordtran's Gastrointestinal and Liver Disease","author":"DS Pratt","year":"2010"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"401","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":"ref32","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":"ref33","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1093\/bioinformatics\/btq419","article-title":"LocusZoom: regional visualization of genome-wide association scan results","volume":"26","author":"RJ Pruim","year":"2010","journal-title":"Bioinformatics"},{"key":"ref34","first-page":"546909","article-title":"Regression Modeling and Meta-Analysis of Diagnostic Accuracy of SNP-Based Pathogenicity Detection Tools for UGT1A1 Gene Mutation","volume":"2013","author":"F Rahim","year":"2013","journal-title":"Genet Res Int"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1093\/hmg\/ddq061","article-title":"Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels","volume":"19","author":"M Barbalic","year":"2010","journal-title":"Hum Mol Genet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1093\/hmg\/ddq057","article-title":"Genetic variants in ABO blood group region, plasma soluble E-selectin levels and risk of type 2 diabetes","volume":"19","author":"L Qi","year":"2010","journal-title":"Hum Mol Genet"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0925-4439(98)00013-1","article-title":"Contribution of two missense mutations (G71R and Y486D) of the bilirubin UDP glycosyltransferase (UGT1A1) gene to phenotypes of Gilbert\u2019s syndrome and Crigler-Najjar syndrome type II","volume":"1406","author":"K Yamamoto","year":"1998","journal-title":"Biochim Biophys Acta"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0009-8981(87)90429-3","article-title":"Specific assays for human alkaline phosphatase isozymes","volume":"166","author":"K Hirano","journal-title":"Clin Chim Acta1987"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0009-8981(80)90295-8","article-title":"Knoth E: Intestinal alkaline phosphatase and the ABO blood group system\u2013a new aspect","volume":"108","author":"PM Bayer","year":"1980","journal-title":"Clin Chim Acta"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1161\/ATVBAHA.109.192971","article-title":"Genome-wide association identifies the ABO blood group as a major locus associated with serum levels of soluble E-selectin","volume":"29","author":"AD Paterson","year":"2009","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/ng.784","article-title":"Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease","volume":"43","author":"H Schunkert","year":"2011","journal-title":"Nat Genet"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1161\/ATVBAHA.107.153262","article-title":"Serum total bilirubin level and prevalent lower extremity peripheral arterial disease: National Health and Nutrition Examination Survey (NHANES) 1999 to 2004","volume":"28","author":"TS Perlstein","year":"2008","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/S0002-9149(01)01962-2","article-title":"Does hyperbilirubinemia protect from coronary heart disease?","volume":"88","author":"L V\u00edtek","year":"2001","journal-title":"Am J Cardiol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0138677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T22:55:33Z","timestamp":1599605733000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0138677"}},"subtitle":[],"editor":[{"given":"Ludmila","family":"Prokunina-Olsson","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,9,28]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2015,9,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0138677","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,28]]}}}