{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T07:33:58Z","timestamp":1767598438333},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Summary: Genome-wide association studies (GWAS) have lead to the identification of hundreds of genomic regions associated with complex diseases. Nevertheless, a large fraction of their heritability remains unexplained. Interaction between genetic variants is one of several putative explanations for the \u2018case of missing heritability\u2019 and, therefore, a compelling next analysis step. However, genome-wide interaction analysis (GWIA) of all pairs of SNPs from a standard marker panel is computationally unfeasible without massive parallelization. Furthermore, GWIA of all SNP triples is utopian. In order to overcome these computational constraints, we present a GWIA approach that selects combinations of SNPs for interaction analysis based on a priori information. Sources of information are statistical evidence (single marker association at a moderate level), genetic relevance (genomic location) and biologic relevance (SNP function class and pathway information). We introduce the software package INTERSNP that implements a logistic regression framework as well as log-linear models for joint analysis of multiple SNPs. Automatic handling of SNP annotation and pathways from the KEGG database is provided. In addition, Monte Carlo simulations to judge genome-wide significance are implemented. We introduce various meaningful GWIA strategies that can be conducted using INTERSNP. Typical examples are, for instance, the analysis of all pairs of non-synonymous SNPs, or, the analysis of all combinations of three SNPs that lie in a common pathway and that are among the top 50 000 single-marker results. We demonstrate the feasibility of these and other GWIA strategies by application to a GWAS dataset and discuss promising results.<\/jats:p>\n               <jats:p>Availability: The software is available at http:\/\/intersnp.meb.uni-bonn.de<\/jats:p>\n               <jats:p>Contact: \u00a0herold@imbie.meb.uni-bonn.de; becker@imbie.meb.uni-bonn.de<\/jats:p>","DOI":"10.1093\/bioinformatics\/btp596","type":"journal-article","created":{"date-parts":[[2009,10,17]],"date-time":"2009-10-17T00:34:09Z","timestamp":1255739649000},"page":"3275-3281","source":"Crossref","is-referenced-by-count":118,"title":["INTERSNP: genome-wide interaction analysis guided by a priori information"],"prefix":"10.1093","volume":"25","author":[{"given":"Christine","family":"Herold","sequence":"first","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 2Department of Genomics, Life & Brain Center, University of Bonn, D-53105 Bonn, 3Institute of Human Genetics, University of Bonn, D-53111 Bonn and 4German Center for Neurodegenerative Diseases (DZNE), D-53105 Bonn, Germany"}]},{"given":"Michael","family":"Steffens","sequence":"additional","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 2Department of Genomics, Life & Brain Center, University of Bonn, D-53105 Bonn, 3Institute of Human Genetics, University of Bonn, D-53111 Bonn and 4German Center for Neurodegenerative Diseases (DZNE), D-53105 Bonn, Germany"}]},{"given":"Felix F.","family":"Brockschmidt","sequence":"additional","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 2Department of Genomics, Life & Brain Center, University of Bonn, D-53105 Bonn, 3Institute of Human Genetics, University of Bonn, D-53111 Bonn and 4German Center for Neurodegenerative Diseases (DZNE), D-53105 Bonn, Germany"},{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 2Department of Genomics, Life & Brain Center, University of Bonn, D-53105 Bonn, 3Institute of Human Genetics, University of Bonn, D-53111 Bonn and 4German Center for Neurodegenerative Diseases (DZNE), D-53105 Bonn, Germany"}]},{"given":"Max P.","family":"Baur","sequence":"additional","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 2Department of Genomics, Life & Brain Center, University of Bonn, D-53105 Bonn, 3Institute of Human Genetics, University of Bonn, D-53111 Bonn and 4German Center for Neurodegenerative Diseases (DZNE), D-53105 Bonn, Germany"},{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 2Department of Genomics, Life & Brain Center, University of Bonn, D-53105 Bonn, 3Institute of Human Genetics, University of Bonn, D-53111 Bonn and 4German Center for Neurodegenerative Diseases (DZNE), D-53105 Bonn, Germany"}]},{"given":"Tim","family":"Becker","sequence":"additional","affiliation":[{"name":"1 Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Str. 25, 2Department of Genomics, Life & Brain Center, University of Bonn, D-53105 Bonn, 3Institute of Human Genetics, University of Bonn, D-53111 Bonn and 4German Center for Neurodegenerative Diseases (DZNE), D-53105 Bonn, Germany"}]}],"member":"286","published-online":{"date-parts":[[2009,10,16]]},"reference":[{"key":"2023013112143784400_B1","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1126\/science.1156409","article-title":"Genetic mapping in human disease","volume":"322","author":"Altshuler","year":"2008","journal-title":"Science"},{"key":"2023013112143784400_B2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.2307\/3001775","article-title":"Tests for linear trends in proportions and frequencies","volume":"11","author":"Armitage","year":"1955","journal-title":"Biometrics"},{"key":"2023013112143784400_B3","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/ejhg.2009.7","article-title":"Joint analysis of tightly linked SNPs in screening step of genome-wide association studies leads to increased power","volume":"17","author":"Becker","year":"2009","journal-title":"Eur. 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