{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:19:33Z","timestamp":1791292773953,"version":"4.1.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T00:00:00Z","timestamp":1298937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3,1]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Reference intervals that incorporate genetic information could reduce the misidentification of unusual test results caused by non\u2013disease-associated genetic variation and increase the detection of results indicating underlying pathology. Subdividing reference groups by genetic effects, however, may lead to increased uncertainty around reference interval endpoints (because of the smaller subgroup sample sizes), thus offsetting any benefits.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We evaluated CLSI guidelines to develop a method appropriate for partitioning reference intervals on the basis of genetic variants with dominant or recessive effects. This method uses information available before reference samples are recruited, thus allowing a preliminary decision regarding partitioning to be made before sampling. We used this method to evaluate the example of Gilbert syndrome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The decision point for partitioning occurs when the percentage of total variance attributable to a dominant or recessive genetic polymorphism exceeds 4%. Similarly, partitioning decision curves are presented based on difference in means between 2 subgroups, sample SD, and subgroup or allele frequency. Laboratory-specific partitioned reference intervals for Gilbert syndrome appear to be statistically warranted for white and African-American populations, but not for Asian populations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>We present a simple method to evaluate whether partitioning based on dominant or recessive genetic effects is statistically justified. Important limitations remain that, in many situations, will preclude integration of genetic, laboratory, and clinical information. As society moves toward personalized medicine, additional research is needed on how to evaluate patient normality while accounting for additive genetic, multigenic, and other multifactorial effects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1373\/clinchem.2010.154005","type":"journal-article","created":{"date-parts":[[2010,12,17]],"date-time":"2010-12-17T04:06:43Z","timestamp":1292558803000},"page":"475-481","source":"Crossref","is-referenced-by-count":9,"title":["Partitioning Reference Intervals by Use of Genetic Information"],"prefix":"10.1093","volume":"57","author":[{"given":"Brian H","family":"Shirts","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R","family":"Wilson","sequence":"first","affiliation":[{"name":"ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R","family":"Jackson","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT"},{"name":"ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,3,1]]},"reference":[{"key":"2020022704535654300_B1","article-title":"Defining, establishing, and verifying reference intervals in the clinical laboratory. 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Case studies on stratifying biochemical reference data by countries using two partitioning methods","volume":"64","author":"Lahti","year":"2004","journal-title":"Scand J Clin Lab Invest"},{"key":"2020022704535654300_B7","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1093\/clinchem\/48.10.1802","article-title":"Effect of ethnicity on reference intervals","volume":"48","author":"Horn","year":"2002","journal-title":"Clin Chem"},{"key":"2020022704535654300_B8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/ng.291","article-title":"Common variants at 30 loci contribute to polygenic dyslipidemia","volume":"41","author":"Kathiresan","year":"2009","journal-title":"Nat Genet"},{"key":"2020022704535654300_B9","doi-asserted-by":"crossref","first-page":"3119","DOI":"10.1002\/sim.1226","article-title":"Reference curves based on non-parametric quantile regression","volume":"21","author":"Gannoun","year":"2002","journal-title":"Stat Med"},{"key":"2020022704535654300_B10","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1002\/(SICI)1097-0258(19980615)17:11<1231::AID-SIM832>3.0.CO;2-E","article-title":"Estimation of age-specific reference ranges via smoother AVAS","volume":"17","author":"Tango","year":"1998","journal-title":"Stat Med"},{"key":"2020022704535654300_B11","first-page":"229","article-title":"Estimation of sex-age specific clinical reference ranges by nonlinear optimization method","volume":"116","author":"Shibata","year":"2005","journal-title":"Stud Health Technol Inform"},{"key":"2020022704535654300_B12","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0021-9150(00)00420-2","article-title":"Association of plasma bilirubin with coronary heart disease and segregation of bilirubin as a major gene trait: the NHLBI family heart study","volume":"154","author":"Hunt","year":"2001","journal-title":"Atherosclerosis"},{"key":"2020022704535654300_B13","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/j.1572-0241.2001.03699.x","article-title":"Correlation of mutational analysis to clinical features in Taiwanese patients with Gilbert's syndrome","volume":"96","author":"Hsieh","year":"2001","journal-title":"Am J Gastroenterol"},{"key":"2020022704535654300_B14","first-page":"259","article-title":"Nonhemolytic unconjugated hyperbilirubinemia with hepatic glucuronyl transferase deficiency: a genetic study in four generations","volume":"80","author":"Sleisenger","year":"1967","journal-title":"Trans Assoc Am Physicians"},{"key":"2020022704535654300_B15","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":"Bosma","year":"1995","journal-title":"N Engl J Med"},{"key":"2020022704535654300_B16","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1124\/dmd.106.014183","article-title":"UDP-glucuronosyltransferase 1A1 gene polymorphisms and total bilirubin levels in an ethnically diverse cohort of women","volume":"35","author":"Hong","year":"2007","journal-title":"Drug Metab Dispos"},{"key":"2020022704535654300_B17","doi-asserted-by":"crossref","first-page":"8170","DOI":"10.1073\/pnas.95.14.8170","article-title":"Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism?","volume":"95","author":"Beutler","year":"1998","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/57\/3\/475\/32655285\/clinchem0475.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/57\/3\/475\/32655285\/clinchem0475.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T09:57:13Z","timestamp":1582797433000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/57\/3\/475\/5621178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,1]]},"references-count":17,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2011,3,1]]},"published-print":{"date-parts":[[2011,3,1]]}},"URL":"https:\/\/doi.org\/10.1373\/clinchem.2010.154005","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,3,1]]},"published":{"date-parts":[[2011,3,1]]}}}