{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:56:20Z","timestamp":1780448180387,"version":"3.54.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In genome-wide association studies, it is widely accepted that multilocus methods are more powerful than testing single-nucleotide polymorphisms (SNPs) one at a time. Among statistical approaches considering many predictors simultaneously, scan statistics are an effective tool for detecting susceptibility genomic regions and mapping disease genes. In this study, inspired by the idea of scan statistics, we propose a novel sliding window-based method for identifying a parsimonious subset of contiguous SNPs that best predict disease status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Within each sliding window, we apply a forward model selection procedure using generalized ridge logistic regression for model fitness in each step. In power simulations, we compare the performance of our method with that of five other methods in current use. Averaging power over all the conditions considered, our method dominates the others. We also present two published datasets where our method is useful in causal SNP identification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our method can automatically combine genetic information in local genomic regions and allow for linkage disequilibrium between SNPs. It can overcome some defects of the scan statistics approach and will be very promising in genome-wide case-control association studies.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2105-12-384","type":"journal-article","created":{"date-parts":[[2011,9,30]],"date-time":"2011-09-30T11:53:17Z","timestamp":1317383597000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Multilocus association mapping using generalized ridge logistic regression"],"prefix":"10.1186","volume":"12","author":[{"given":"Zhe","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurg","family":"Ott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,9,29]]},"reference":[{"key":"4837_CR1","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nrg1155","volume":"4","author":"J Hoh","year":"2003","unstructured":"Hoh J, Ott J: Mathematical multi-locus approaches to localizing complex human trait genes. Nat Rev Genet 2003, 4: 701\u2013709.","journal-title":"Nat Rev Genet"},{"key":"4837_CR2","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/nrg2344","volume":"9","author":"MI McCarthy","year":"2008","unstructured":"McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JPA, Hirschhorn JN: Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 2008, 9: 356\u2013369. 10.1038\/nrg2344","journal-title":"Nat Rev Genet"},{"key":"4837_CR3","first-page":"4","volume-title":"PLoS Genet","author":"CJ Hoggart","year":"2008","unstructured":"Hoggart CJ, Whittaker JC, De Iorio M, Balding DJ: Simultaneous analysis of all SNPs in genome-wide and re-sequencing association studies. PLoS Genet 2008, 4."},{"key":"4837_CR4","doi-asserted-by":"publisher","first-page":"9615","DOI":"10.1073\/pnas.170179197","volume":"97","author":"J Hoh","year":"2000","unstructured":"Hoh J, Ott J: Scan statistics to scan markers for susceptibility genes. Proc Natl Acad Sci USA 2000, 97: 9615\u20139617.","journal-title":"Proc Natl Acad Sci USA"},{"key":"4837_CR5","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1002\/gepi.0042","volume":"22","author":"DV Zaykin","year":"2002","unstructured":"Zaykin DV, Zhivotovsky LA, Westfall PH, Weir BS: Truncated product method for combining P-values. Genet Epidemiol 2002, 22: 170\u2013185. 10.1002\/gepi.0042","journal-title":"Genet Epidemiol"},{"key":"4837_CR6","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1002\/gepi.10264","volume":"25","author":"F Dudbridge","year":"2003","unstructured":"Dudbridge F, Koeleman BP: Rank truncated product of P-values, with application to genomewide association scans. Genetic Epidemiology 2003, 25: 360\u2013366. 10.1002\/gepi.10264","journal-title":"Genetic Epidemiology"},{"key":"4837_CR7","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1534\/genetics.107.084616","volume":"179","author":"H Yang","year":"2008","unstructured":"Yang H, Hsieh H, Fann CSJ: Kernel-based association test. Genetics 2008, 179: 1057\u20131068. 10.1534\/genetics.107.084616","journal-title":"Genetics"},{"key":"4837_CR8","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1002\/gepi.20173","volume":"30","author":"YV Sun","year":"2006","unstructured":"Sun YV, Levin AM, Boerwinkle E, Robertson H, Kardia SL: A scan statistic for identifying chromosomal patterns of SNP association. Genetic Epidemiology 2006, 30: 627\u2013635. 10.1002\/gepi.20173","journal-title":"Genetic Epidemiology"},{"key":"4837_CR9","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1086\/503876","volume":"78","author":"SR Browning","year":"2006","unstructured":"Browning SR: Multilocus association mapping using variable-Length markov chains. Am J Hum Genet 2006, 78: 903\u2013913. 10.1086\/503876","journal-title":"Am J Hum Genet"},{"key":"4837_CR10","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1086\/513205","volume":"80","author":"Y Li","year":"2007","unstructured":"Li Y, Sung W, Liu JJ: Association mapping via regularized regression analysis of single-nucleotide-polymorphism haplotypes in variable-sized sliding windows. Am J Hum Genet 2007, 80: 705\u2013715. 10.1086\/513205","journal-title":"Am J Hum Genet"},{"key":"4837_CR11","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/biostatistics\/kxm010","volume":"9","author":"MY Park","year":"2008","unstructured":"Park MY, Hastie T: Penalized logistic regression for detecting gene interactions. Biostat 2008, 9: 30\u201350.","journal-title":"Biostat"},{"key":"4837_CR12","first-page":"191","volume":"41","author":"SL Cessie","year":"1992","unstructured":"Cessie SL, Houwelingen JCV: Ridge estimators in logistic regression. Journal of the Royal Statistical Society Series C (Applied Statistics) 1992, 41: 191\u2013201.","journal-title":"Journal of the Royal Statistical Society Series C (Applied Statistics)"},{"key":"4837_CR13","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.ajhg.2007.10.012","volume":"82","author":"N Malo","year":"2008","unstructured":"Malo N, Libiger O, Schork NJ: Accommodating linkage disequilibrium in genetic-association analyses via ridge regression. Am J Hum Genet 2008, 82: 375\u2013385. 10.1016\/j.ajhg.2007.10.012","journal-title":"Am J Hum Genet"},{"key":"4837_CR14","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1080\/01621459.1992.10476248","volume":"87","author":"RJ Gray","year":"1992","unstructured":"Gray RJ: Flexible methods for analyzing survival data using splines, With applications to breast cancer prognosis. Journal of the American Statistical Association 1992, 87: 942\u2013951. 10.2307\/2290630","journal-title":"Journal of the American Statistical Association"},{"key":"4837_CR15","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1109\/TAC.1974.1100733","volume":"19","author":"H Akaike","year":"1974","unstructured":"Akaike H: A new look at the statistical model identification. Automatic Control, IEEE Transactions on 1974, 19: 723. 716 716 10.1109\/TAC.1974.1100733","journal-title":"Automatic Control, IEEE Transactions on"},{"key":"4837_CR16","volume-title":"Statistical methods for research workers","author":"RA Fisher","year":"1970","unstructured":"Fisher RA: Statistical methods for research workers. 14th edition. New York: Oliver and Boyd; 1970.","edition":"14"},{"key":"4837_CR17","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","volume":"58","author":"R Tibshirani","year":"1996","unstructured":"Tibshirani R: Regression shrinkage and selection via the lasso. Journal of the Royal Statistical Society Series B (Methodological) 1996, 58: 267\u2013288.","journal-title":"Journal of the Royal Statistical Society Series B (Methodological)"},{"key":"4837_CR18","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1093\/bioinformatics\/btp041","volume":"25","author":"TT Wu","year":"2009","unstructured":"Wu TT, Chen YF, Hastie T, Sobel E, Lange K: Genome-wide association analysis by lasso penalized logistic regression. Bioinformatics 2009, 25: 714\u2013721. 10.1093\/bioinformatics\/btp041","journal-title":"Bioinformatics"},{"key":"4837_CR19","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/j.1467-9868.2005.00503.x","volume":"67","author":"H Zou","year":"2005","unstructured":"Zou H, Hastie T: Regularization and variable selection via the elastic net. Journal of the Royal Statistical Society Series B 2005, 67: 301\u2013320. 10.1111\/j.1467-9868.2005.00503.x","journal-title":"Journal of the Royal Statistical Society Series B"},{"key":"4837_CR20","doi-asserted-by":"publisher","first-page":"S25","DOI":"10.1186\/1753-6561-3-s7-s25","volume":"3","author":"S Cho","year":"2009","unstructured":"Cho S, Kim H, Oh S, Kim K, Park T: Elastic-net regularization approaches for genome-wide association studies of rheumatoid arthritis. BMC Proceedings 2009, 3: S25.","journal-title":"BMC Proceedings"},{"key":"4837_CR21","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/gepi.20459","volume":"34","author":"J Wu","year":"2010","unstructured":"Wu J, Devlin B, Ringquist S, Trucco M, Roeder K: Screen and clean: a tool for identifying interactions in genome-wide association studies. Genetic Epidemiology 2010, 34: 275\u2013285.","journal-title":"Genetic Epidemiology"},{"key":"4837_CR22","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/gepi.10237","volume":"25","author":"B Devlin","year":"2003","unstructured":"Devlin B, Roeder K, Wasserman L: Analysis of multilocus models of association. Genetic Epidemiology 2003, 25: 36\u201347. 10.1002\/gepi.10237","journal-title":"Genetic Epidemiology"},{"key":"4837_CR23","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/sj.mp.4002147","volume":"13","author":"DA Nielsen","year":"2008","unstructured":"Nielsen DA, Ji F, Yuferov V, Ho A, Chen A, Levran O, Ott J, Kreek MJ: Genotype patterns that contribute to increased risk for or protection from developing heroin addiction. Mol Psychiatry 2008, 13: 417\u2013428. 10.1038\/sj.mp.4002147","journal-title":"Mol Psychiatry"},{"key":"4837_CR24","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1126\/science.1133807","volume":"314","author":"A DeWan","year":"2006","unstructured":"DeWan A, Liu M, Hartman S, Zhang SS, Liu DTL, Zhao C, Tam POS, Chan WM, Lam DSC, Snyder M, Barnstable C, Pang CP, Hoh J: HTRA1 promoter polymorphism in wet age-related macular degeneration. Science 2006, 314: 989\u2013992. 10.1126\/science.1133807","journal-title":"Science"},{"key":"4837_CR25","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1126\/science.1109557","volume":"308","author":"RJ Klein","year":"2005","unstructured":"Klein RJ, Zeiss C, Chew EY, Tsai J, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J: Complement factor H polymorphism in age-related macular degeneration. Science 2005, 308: 385\u2013389. 10.1126\/science.1109557","journal-title":"Science"},{"key":"4837_CR26","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. The American Journal of Human Genetics 2007, 81: 559\u2013575. 10.1086\/519795","journal-title":"The American Journal of Human Genetics"},{"key":"4837_CR27","volume-title":"R: a language and environment for statistical computing","author":"R Development Core Team","year":"2010","unstructured":"R Development Core Team: R: a language and environment for statistical computing. Vienna, Austria; 2010."},{"key":"4837_CR28","volume-title":"Design: R package version 2.3-0","author":"FE Harrell","year":"2009","unstructured":"Harrell FE: Design: R package version 2.3\u20130. 2009."},{"key":"4837_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","volume":"33","author":"J Friedman","year":"2010","unstructured":"Friedman J, Hastie T, Tibshirani R: Regularization paths for generalized linear models via coordinate descent. Journal of Statistical Software 2010, 33: 1\u201322.","journal-title":"Journal of Statistical Software"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-12-384.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T02:51:41Z","timestamp":1712976701000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-12-384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,9,29]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["4837"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-12-384","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,9,29]]},"assertion":[{"value":"16 October 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2011","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"384"}}