{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:35:49Z","timestamp":1772714149835,"version":"3.50.1"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1490,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: For the past few decades, many statistical methods in genome-wide association studies (GWAS) have been developed to identify SNP\u2013SNP interactions for case-control studies. However, there has been less work for prospective cohort studies, involving the survival time. Recently, Gui et al. (2011) proposed a novel method, called Surv-MDR, for detecting gene\u2013gene interactions associated with survival time. Surv-MDR is an extension of the multifactor dimensionality reduction (MDR) method to the survival phenotype by using the log-rank test for defining a binary attribute. However, the Surv-MDR method has some drawbacks in the sense that it needs more intensive computations and does not allow for a covariate adjustment. In this article, we propose a new approach, called Cox-MDR, which is an extension of the generalized multifactor dimensionality reduction (GMDR) to the survival phenotype by using a martingale residual as a score to classify multi-level genotypes as high- and low-risk groups. The advantages of Cox-MDR over Surv-MDR are to allow for the effects of discrete and quantitative covariates in the frame of Cox regression model and to require less computation than Surv-MDR.<\/jats:p><jats:p>Results: Through simulation studies, we compared the power of Cox-MDR with those of Surv-MDR and Cox regression model for various heritability and minor allele frequency combinations without and with adjusting for covariate. We found that Cox-MDR and Cox regression model perform better than Surv-MDR for low minor allele frequency of 0.2, but Surv-MDR has high power for minor allele frequency of 0.4. However, when the effect of covariate is adjusted for, Cox-MDR and Cox regression model perform much better than Surv-MDR. We also compared the performance of Cox-MDR and Surv-MDR for a real data of leukemia patients to detect the gene\u2013gene interactions with the survival time.<\/jats:p><jats:p>Contact: \u00a0leesy@sejong.ac.kr; tspark@snu.ac.kr<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts415","type":"journal-article","created":{"date-parts":[[2012,9,7]],"date-time":"2012-09-07T20:35:22Z","timestamp":1347050122000},"page":"i582-i588","source":"Crossref","is-referenced-by-count":39,"title":["Gene\u2013gene interaction analysis for the survival phenotype based on the Cox model"],"prefix":"10.1093","volume":"28","author":[{"given":"Seungyeoun","family":"Lee","sequence":"first","affiliation":[{"name":"1 Department of Mathematics and Statistics, Sejong University, Seoul 143-747"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Seok","family":"Kwon","sequence":"additional","affiliation":[{"name":"2 Interdisciplinary Program in Bioinformatics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Mi","family":"Oh","sequence":"additional","affiliation":[{"name":"3 College of Pharmacy and Research Institute of Pharmaceutical Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taesung","family":"Park","sequence":"additional","affiliation":[{"name":"2 Interdisciplinary Program in Bioinformatics"},{"name":"4 Department of Statistics, Seoul National University, Seoul 151-747, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,9,3]]},"reference":[{"key":"2023012513060733700_B1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s00439-009-0645-6","article-title":"Bladder cancer SNP panel predicts susceptibility and survival","volume":"125","author":"Andrew","year":"2009","journal-title":"Hum. 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