{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T07:14:14Z","timestamp":1711955654732},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2150,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Summary: It has been argued that the missing heritability in common diseases may be in part due to rare variants and gene\u2013gene effects. Haplotype analyses provide more power for rare variants and joint analyses across genes can address multi-gene effects. Currently, methods are lacking to perform joint multi-locus association analyses across more than one gene\/region. Here, we present a haplotype-mining gene\u2013gene analysis method, which considers multi-locus data for two genes\/regions simultaneously. This approach extends our single region haplotype-mining algorithm, hapConstructor, to two genes\/regions. It allows construction of multi-locus SNP sets at both genes and tests joint gene\u2013gene effects and interactions between single variants or haplotype combinations. A Monte Carlo framework is used to provide statistical significance assessment of the joint and interaction statistics, thus the method can also be used with related individuals. This tool provides a flexible data-mining approach to identifying gene\u2013gene effects that otherwise is currently unavailable.<\/jats:p><jats:p>Availability: \u00a0http:\/\/bioinformatics.med.utah.edu\/Genie\/hapConstructor.html<\/jats:p><jats:p>Contact: \u00a0ryan.abo@hsc.utah.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq616","type":"journal-article","created":{"date-parts":[[2010,11,14]],"date-time":"2010-11-14T01:26:18Z","timestamp":1289697978000},"page":"134-136","source":"Crossref","is-referenced-by-count":1,"title":["Automated construction and testing of multi-locus gene\u2013gene associations"],"prefix":"10.1093","volume":"27","author":[{"given":"Ryan","family":"Abo","sequence":"first","affiliation":[{"name":"1 Department of Biomedical Informatics and 2Department of Internal Medicine, University of Utah School of Medicine, UT, USA"}]},{"given":"Stacey","family":"Knight","sequence":"additional","affiliation":[{"name":"1 Department of Biomedical Informatics and 2Department of Internal Medicine, University of Utah School of Medicine, UT, USA"}]},{"given":"Alun","family":"Thomas","sequence":"additional","affiliation":[{"name":"1 Department of Biomedical Informatics and 2Department of Internal Medicine, University of Utah School of Medicine, UT, USA"}]},{"given":"Nicola J.","family":"Camp","sequence":"additional","affiliation":[{"name":"1 Department of Biomedical Informatics and 2Department of Internal Medicine, University of Utah School of Medicine, UT, USA"}]}],"member":"286","published-online":{"date-parts":[[2010,11,13]]},"reference":[{"key":"2023012511160175900_B1","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1093\/bioinformatics\/btn359","article-title":"hapConstructor: automatic construction and testing of haplotypes in a Monte Carlo framework","volume":"24","author":"Abo","year":"2008","journal-title":"Bioinformatics"},{"key":"2023012511160175900_B2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/1471-2105-7-209","article-title":"PedGenie: an analysis approach for genetic association testing in extended pedigrees and genealogies of arbitrary size","volume":"7","author":"Allen-Brady","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023012511160175900_B3","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/gepi.20096","article-title":"Haplotype interaction analysis of unlinked regions","volume":"29","author":"Becker","year":"2005","journal-title":"Genet. Epidemiol."},{"key":"2023012511160175900_B4","first-page":"365","article-title":"Efficient multilocus association testing for whole genome association studies using localized haplotype clustering","volume":"375","author":"Browning","year":"2007","journal-title":"Power"},{"key":"2023012511160175900_B5","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1086\/503876","article-title":"Multilocus association mapping using variable-length Markov chains","volume":"78","author":"Browning","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"2023012511160175900_B6","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/gepi.20025","article-title":"The role of haplotypes in candidate gene studies","volume":"27","author":"Clark","year":"2004","journal-title":"Genet. 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Hered."},{"key":"2023012511160175900_B15","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/gepi.20037","article-title":"Evaluating associations of haplotypes with traits","volume":"27","author":"Schaid","year":"2004","journal-title":"Genet. Epidemiol."},{"key":"2023012511160175900_B16","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195159394.001.0001","volume-title":"Statistical Methods in Genetic Epidemiology","author":"Thomas","year":"2004"},{"key":"2023012511160175900_B17","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1086\/521558","article-title":"Haplotype-based association analysis via variance-components score test","volume":"81","author":"Tzeng","year":"2007","journal-title":"Am. J. Hum. 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