{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:22:30Z","timestamp":1765545750340},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Canonical correlation analysis (CCA) measures the association between two sets of multidimensional variables. We reasoned that CCA could provide an efficient and powerful approach for both univariate and multivariate gene-based tests of association without the need for permutation testing.<\/jats:p>\n               <jats:p>Results: Compared with a commonly used permutation-based approach, CCA (i) is faster; (ii) has appropriate type-I error rate for normally distributed quantitative traits; (iii) provides comparable power for small to medium-sized genes (&amp;lt;100 kb); (iv) provides greater power when the causal variants are uncommon; (v) provides considerably less power for larger genes (\u2265100 kb) when the causal variants have a broad minor allele frequency (MAF) spectrum. Application to a GWAS of leukocyte levels identified SAFB and a histone gene cluster as novel putative loci harboring multiple independent variants regulating lymphocyte and neutrophil counts.<\/jats:p>\n               <jats:p>Availability: \u00a0http:\/\/genepi.qimr.edu.au\/staff\/manuelF\/gene\/main.html<\/jats:p>\n               <jats:p>Contact: \u00a0manuel.ferreira@qimr.edu.au<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary material is available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts051","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T17:01:11Z","timestamp":1328202071000},"page":"845-850","source":"Crossref","is-referenced-by-count":64,"title":["A gene-based test of association using canonical correlation analysis"],"prefix":"10.1093","volume":"28","author":[{"given":"Clara S.","family":"Tang","sequence":"first","affiliation":[{"name":"Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia"}]},{"given":"Manuel A. R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia"}]}],"member":"286","published-online":{"date-parts":[[2012,1,31]]},"reference":[{"key":"2023012512200256300_B1","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1086\/302038","article-title":"Multiple phenotype modeling in gene-mapping studies of quantitative traits: power advantages","volume":"63","author":"Allison","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"2023012512200256300_B2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000053334","article-title":"Comparison of multivariate tests for genetic linkage","volume":"51","author":"Amos","year":"2001","journal-title":"Hum. Hered."},{"key":"2023012512200256300_B3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1023\/B:BEGE.0000013727.15845.f8","article-title":"A simulation study concerning the effect of varying the residual phenotypic correlation on the power of bivariate quantitative trait loci linkage analysis","volume":"34","author":"Evans","year":"2004","journal-title":"Behav. Genet."},{"key":"2023012512200256300_B4","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.ajhg.2009.10.005","article-title":"Sequence variants in three loci influence monocyte counts and erythrocyte volume","volume":"85","author":"Ferreira","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"2023012512200256300_B5","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1093\/bioinformatics\/btn563","article-title":"A multivariate test of association","volume":"25","author":"Ferreira","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012512200256300_B6","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/jcb.22420","article-title":"SAFB1's multiple functions in biological control-lots still to be done!","volume":"109","author":"Garee","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"2023012512200256300_B7","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1074\/jbc.M109.066431","article-title":"SAFB1 mediates repression of immune regulators and apoptotic genes in breast cancer cells","volume":"285","author":"Hammerich-Hille","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2023012512200256300_B8","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/biomet\/28.3-4.321","article-title":"Relations between 2 sets of variables","volume":"28","author":"Hotelling","year":"1936","journal-title":"Biometrika"},{"key":"2023012512200256300_B9","doi-asserted-by":"crossref","first-page":"e1002177","DOI":"10.1371\/journal.pgen.1002177","article-title":"Gene-based tests of association","volume":"7","author":"Huang","year":"2011","journal-title":"PLoS Genet."},{"key":"2023012512200256300_B10","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1093\/bioinformatics\/btm138","article-title":"GENOME: a rapid coalescent-based whole genome simulator","volume":"23","author":"Liang","year":"2007","journal-title":"Bioinformatics"},{"key":"2023012512200256300_B11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ajhg.2010.06.009","article-title":"A versatile gene-based test for genome-wide association studies","volume":"87","author":"Liu","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"2023012512200256300_B12","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa0906312","article-title":"A large-scale, consortium-based genomewide association study of asthma","volume":"363","author":"Moffatt","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"2023012512200256300_B13","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1086\/423901","article-title":"The future of association studies: gene-based analysis and replication","volume":"75","author":"Neale","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"2023012512200256300_B14","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1139\/o06-082","article-title":"Beyond the walls of the nucleus: the role of histones in cellular signaling and innate immunity","volume":"84","author":"Parseghian","year":"2006","journal-title":"Biochem. Cell Biol."},{"key":"2023012512200256300_B15","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/nature08872","article-title":"Understanding mechanisms underlying human gene expression variation with RNA sequencing","volume":"464","author":"Pickrell","year":"2010","journal-title":"Nature"},{"key":"2023012512200256300_B16","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":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2023012512200256300_B17","doi-asserted-by":"crossref","first-page":"e1001053","DOI":"10.1371\/journal.pgen.1001053","article-title":"Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD","volume":"6","author":"Saccone","year":"2010","journal-title":"PLoS Genet"},{"key":"2023012512200256300_B18","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/ng.275","article-title":"Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study","volume":"41","author":"Silverberg","year":"2009","journal-title":"Nat. Genet."},{"key":"2023012512200256300_B19","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1038\/nm.2053","article-title":"Extracellular histones are major mediators of death in sepsis","volume":"15","author":"Xu","year":"2009","journal-title":"Nat. Med."},{"key":"2023012512200256300_B20","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1093\/jnci\/djm169","article-title":"Association between two unlinked loci at 8q24 and prostate cancer risk among European Americans","volume":"99","author":"Zheng","year":"2007","journal-title":"J. Natl Cancer. Inst."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/6\/845\/48875914\/bioinformatics_28_6_845.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/6\/845\/48875914\/bioinformatics_28_6_845.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T15:36:08Z","timestamp":1674660968000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/28\/6\/845\/312636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,31]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,3,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bts051","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,3,15]]},"published":{"date-parts":[[2012,1,31]]}}}