{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T16:43:57Z","timestamp":1758127437028},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation : Meta-analysis of summary statistics is an essential approach to guarantee the success of genome-wide association studies (GWAS). Application of the fixed or random effects model to single-marker association tests is a standard practice. More complex methods of meta-analysis involving multiple parameters have not been used frequently, a gap that could be explained by the lack of a respective meta-analysis pipeline. Meta-analysis based on combining p -values can be applied to any association test. However, to be powerful, meta-analysis methods for high-dimensional models should incorporate additional information such as study-specific properties of parameter estimates, their effect directions, standard errors and covariance structure.<\/jats:p><jats:p>Results : We modified \u2018method for the synthesis of linear regression slopes\u2019 recently proposed in the educational sciences to the case of multiple logistic regression, and implemented it in a meta-analysis tool called METAINTER. The software handles models with an arbitrary number of parameters, and can directly be applied to analyze the results of single-SNP tests, global haplotype tests, tests for and under gene\u2013gene or gene\u2013environment interaction. Via simulations for two-single nucleotide polymorphisms (SNP) models we have shown that the proposed meta-analysis method has correct type I error rate. Moreover, power estimates come close to that of the joint analysis of the entire sample. We conducted a real data analysis of six GWAS of type 2 diabetes, available from dbGaP ( http:\/\/www.ncbi.nlm.nih.gov\/gap ). For each study, a genome-wide interaction analysis of all SNP pairs was performed by logistic regression tests. The results were then meta-analyzed with METAINTER.<\/jats:p><jats:p>Availability : The software is freely available and distributed under the conditions specified on http:\/\/metainter.meb.uni-bonn.de<\/jats:p><jats:p>Contact : vait@imbie.meb.uni-bonn.de<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btu629","type":"journal-article","created":{"date-parts":[[2014,9,25]],"date-time":"2014-09-25T00:36:59Z","timestamp":1411605419000},"page":"151-157","source":"Crossref","is-referenced-by-count":5,"title":["METAINTER: meta-analysis of multiple regression models in genome-wide association studies"],"prefix":"10.1093","volume":"31","author":[{"given":"Tatsiana","family":"Vaitsiakhovich","sequence":"first","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and 2 German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany"},{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and 2 German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitriy","family":"Drichel","sequence":"additional","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and 2 German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Herold","sequence":"additional","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and 2 German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Lacour","sequence":"additional","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and 2 German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Becker","sequence":"additional","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and 2 German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany"},{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn and 2 German Center for Neurodegenerative Diseases (DZNE), Sigmund-Freud-Str. 25, D-53105 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,9,23]]},"reference":[{"key":"2023020116140424500_btu629-B1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.4239\/wjd.v4.i4.114","article-title":"Genetics of type 2 diabetes","volume":"4","author":"Ali","year":"2013","journal-title":"World J. 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Statist. Soc."},{"key":"2023020116140424500_btu629-B9","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrg3472","article-title":"Meta-analysis methods for genome-wide association studies and beyond","volume":"14","author":"Evangelou","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"2023020116140424500_btu629-B10","volume-title":"Statistical Methods for Research Workers","author":"Fisher","year":"1932"},{"key":"2023020116140424500_btu629-B11","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1093\/bioinformatics\/btp596","article-title":"INTERSNP: genome-wide interaction analysis guided by a priori information","volume":"25","author":"Herold","year":"2009","journal-title":"Bioinformatics"},{"key":"2023020116140424500_btu629-B12","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1159\/000336196","article-title":"Integrated genome-wide pathway association analysis with INTERSNP","volume":"73","author":"Herold","year":"2012","journal-title":"Hum. 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