{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T17:28:45Z","timestamp":1745947725962},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"19","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"Abstract<\/jats:title>\n Summary: Genetic correlations are the genome-wide aggregate effects of causal variants affecting multiple traits. Traditionally, genetic correlations between complex traits are estimated from pedigree studies, but such estimates can be confounded by shared environmental factors. Moreover, for diseases, low prevalence rates imply that even if the true genetic correlation between disorders was high, co-aggregation of disorders in families might not occur or could not be distinguished from chance. We have developed and implemented statistical methods based on linear mixed models to obtain unbiased estimates of the genetic correlation between pairs of quantitative traits or pairs of binary traits of complex diseases using population-based case\u2013control studies with genome-wide single-nucleotide polymorphism data. The method is validated in a simulation study and applied to estimate genetic correlation between various diseases from Wellcome Trust Case Control Consortium data in a series of bivariate analyses. We estimate a significant positive genetic correlation between risk of Type 2 diabetes and hypertension of ~0.31 (SE 0.14, P = 0.024).<\/jats:p>\n Availability: Our methods, appropriate for both quantitative and binary traits, are implemented in the freely available software GCTA (http:\/\/www.complextraitgenomics.com\/software\/gcta\/reml_bivar.html).<\/jats:p>\n Contact: \u00a0hong.lee@uq.edu.au<\/jats:p>\n Supplementary Information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts474","type":"journal-article","created":{"date-parts":[[2012,7,28]],"date-time":"2012-07-28T10:52:46Z","timestamp":1343472766000},"page":"2540-2542","source":"Crossref","is-referenced-by-count":556,"title":["Estimation of pleiotropy between complex diseases using single-nucleotide polymorphism-derived genomic relationships and restricted maximum likelihood"],"prefix":"10.1093","volume":"28","author":[{"given":"S.H.","family":"Lee","sequence":"first","affiliation":[{"name":"1 The University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, 2The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, QLD 4102 and 3Department of Agriculture and Food Systems, University of Melbourne, VIC 3010, Melbourne, Australia"}]},{"given":"J.","family":"Yang","sequence":"additional","affiliation":[{"name":"1 The University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, 2The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, QLD 4102 and 3Department of Agriculture and Food Systems, University of Melbourne, VIC 3010, Melbourne, Australia"}]},{"given":"M.E.","family":"Goddard","sequence":"additional","affiliation":[{"name":"1 The University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, 2The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, QLD 4102 and 3Department of Agriculture and Food Systems, University of Melbourne, VIC 3010, Melbourne, Australia"}]},{"given":"P.M.","family":"Visscher","sequence":"additional","affiliation":[{"name":"1 The University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, 2The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, QLD 4102 and 3Department of Agriculture and Food Systems, University of Melbourne, VIC 3010, Melbourne, Australia"},{"name":"1 The University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, 2The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, QLD 4102 and 3Department of Agriculture and Food Systems, University of Melbourne, VIC 3010, Melbourne, Australia"}]},{"given":"N.R.","family":"Wray","sequence":"additional","affiliation":[{"name":"1 The University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, 2The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, QLD 4102 and 3Department of Agriculture and Food Systems, University of Melbourne, VIC 3010, Melbourne, Australia"}]}],"member":"286","published-online":{"date-parts":[[2012,7,26]]},"reference":[{"key":"2023012513055627300_bts474-B1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/genetics\/35.2.212","article-title":"Heritability of threshold characters","volume":"35","author":"Dempster","year":"1950","journal-title":"Genetics"},{"key":"2023012513055627300_bts474-B2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/j.1469-1809.1965.tb00500.x","article-title":"The inheritance of liability to certain diseases, estimated from the incidence among relatives","volume":"29","author":"Falconer","year":"1965","journal-title":"Ann. 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Genet."},{"key":"2023012513055627300_bts474-B6","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3168\/jds.S0022-0302(95)76654-1","article-title":"Restricted maximum likelihood estimation of variance components for univariate animal models using sparse matrix techniques and average information","volume":"78","author":"Johnson","year":"1995","journal-title":"J. Dairy Sci."},{"key":"2023012513055627300_bts474-B7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/ng.1108","article-title":"Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs","volume":"44","author":"Lee","year":"2012","journal-title":"Nat. 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Genet."},{"key":"2023012513055627300_bts474-B10","doi-asserted-by":"crossref","first-page":"527","DOI":"10.2307\/2529174","article-title":"The estimation of variance and covariance components with an application when records are subject to culling","volume":"29","author":"Thompson","year":"1973","journal-title":"Biometrics"},{"key":"2023012513055627300_bts474-B11","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/ejhg.2011.257","article-title":"Impact of diagnostic misclassification on estimation of genetic correlations using genome-wide genotypes","volume":"20","author":"Wray","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"2023012513055627300_bts474-B12","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","article-title":"Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls","volume":"447","author":"WTCCC","year":"2007","journal-title":"Nature"},{"key":"2023012513055627300_bts474-B13","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/ng.608","article-title":"Common SNPs explain a large proportion of the heritability for human height","volume":"42","author":"Yang","year":"2010","journal-title":"Nat. Genet."},{"key":"2023012513055627300_bts474-B14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: a tool for genome-wide complex trait analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am. J. Hum. Genet."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/19\/2540\/48879715\/bioinformatics_28_19_2540.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/19\/2540\/48879715\/bioinformatics_28_19_2540.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T18:57:19Z","timestamp":1674673039000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/28\/19\/2540\/289604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,26]]},"references-count":14,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2012,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bts474","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,10,1]]},"published":{"date-parts":[[2012,7,26]]}}}