{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:30:08Z","timestamp":1780511408331,"version":"3.54.1"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T00:00:00Z","timestamp":1431302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>In genetic association studies of an ordered categorical phenotype, it is usual to either regroup multiple categories of the phenotype into two categories and then apply the logistic regression<jats:bold>(LG)<\/jats:bold>, or apply ordered logistic<jats:bold>(oLG)<\/jats:bold>, or ordered probit<jats:bold>(oPRB)<\/jats:bold>regression, which accounts for the ordinal nature of the phenotype. However, they may lose statistical power or may not control type I error due to their model assumption and\/or instable parameter estimation algorithm when the genetic variant is rare or sample size is limited. To solve this problem, we propose a set\u2010valued<jats:bold>(SV)<\/jats:bold>system model to identify genetic variants associated with an ordinal categorical phenotype. We couple this model with a SV system identification algorithm to identify all the key system parameters. Simulations and two real data analyses show that<jats:bold>SV<\/jats:bold>and<jats:bold>LG<\/jats:bold>accurately controlled the Type I error rate even at a significance level of 10<jats:sup>\u22126<\/jats:sup>but not<jats:bold>oLG<\/jats:bold>and<jats:bold>oPRB<\/jats:bold>in some cases.<jats:bold>LG<\/jats:bold>had significantly less power than the other three methods due to disregarding of the ordinal nature of the phenotype, and<jats:bold>SV<\/jats:bold>had similar or greater power than<jats:bold>oLG<\/jats:bold>and<jats:bold>oPRB<\/jats:bold>. We argue that<jats:bold>SV<\/jats:bold>should be employed in genetic association studies for ordered categorical phenotype.<\/jats:p>","DOI":"10.1111\/ahg.12117","type":"journal-article","created":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T08:18:23Z","timestamp":1431332303000},"page":"294-309","source":"Crossref","is-referenced-by-count":10,"title":["SVSI: Fast and Powerful Set\u2010Valued System Identification Approach to Identifying Rare Variants in Sequencing Studies for Ordered Categorical Traits"],"prefix":"10.1111","volume":"79","author":[{"given":"Wenjian","family":"Bi","sequence":"first","affiliation":[{"name":"Key Laboratory of Systems and Control, Academy of Mathematics and Systems Science Chinese Academy of Sciences Beijing 100190 P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Statistics and Probability Michigan State University East Lansing MI 48824 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Genetics, Department of Biostatistics University of North Carolina Chapel Hill NC 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetics, Department of Biostatistics University of North Carolina Chapel Hill NC 27599 USA"},{"name":"Department of Computer Science University of North Carolina Chapel Hill NC 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital Memphis TN 38105 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley B.","family":"Pounds","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital Memphis TN 38105 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Borowitz","sequence":"additional","affiliation":[{"name":"Johns Hopkins Medical Institute Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary V.","family":"Relling","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis TN 38105 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun J.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences St. Jude Children's Research Hospital Memphis TN 38105 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifa","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics St. Jude Children's Research Hospital Memphis TN 38105 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Hon","family":"Pui","sequence":"additional","affiliation":[{"name":"Department of Oncology St. Jude Children's Research Hospital Memphis TN 38105 USA"},{"name":"Department of Pediatrics University of Tennessee Health Science Center Memphis TN 38163 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Hunger","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine and Children's Hospital Colorado Aurora CO 80045 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Hartford","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation and Cellular Therapy St. Jude Children's Research Hospital Memphis TN 38105 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Bone Marrow Transplantation and Cellular Therapy St. Jude Children's Research Hospital Memphis TN 38105 USA"},{"name":"Department of Pediatrics University of Tennessee Health Science Center Memphis TN 38163 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systems and Control, Academy of Mathematics and Systems Science Chinese Academy of Sciences Beijing 100190 P.R. 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