{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:21:05Z","timestamp":1778599265617,"version":"3.51.4"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2451,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Epistasis, the presence of gene\u2013gene interactions, has been hypothesized to be at the root of many common human diseases, but current genome-wide association studies largely ignore its role. Multifactor dimensionality reduction (MDR) is a powerful model-free method for detecting epistatic relationships between genes, but computational costs have made its application to genome-wide data difficult. Graphics processing units (GPUs), the hardware responsible for rendering computer games, are powerful parallel processors. Using GPUs to run MDR on a genome-wide dataset allows for statistically rigorous testing of epistasis.<\/jats:p>\n               <jats:p>Results: The implementation of MDR for GPUs (MDRGPU) includes core features of the widely used Java software package, MDR. This GPU implementation allows for large-scale analysis of epistasis at a dramatically lower cost than the standard CPU-based implementations. As a proof-of-concept, we applied this software to a genome-wide study of sporadic amyotrophic lateral sclerosis (ALS). We discovered a statistically significant two-SNP classifier and subsequently replicated the significance of these two SNPs in an independent study of ALS. MDRGPU makes the large-scale analysis of epistasis tractable and opens the door to statistically rigorous testing of interactions in genome-wide datasets.<\/jats:p>\n               <jats:p>Availability: MDRGPU is open source and available free of charge from http:\/\/www.sourceforge.net\/projects\/mdr.<\/jats:p>\n               <jats:p>Contact: \u00a0jason.h.moore@dartmouth.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq009","type":"journal-article","created":{"date-parts":[[2010,1,17]],"date-time":"2010-01-17T01:25:18Z","timestamp":1263691518000},"page":"694-695","source":"Crossref","is-referenced-by-count":66,"title":["Multifactor dimensionality reduction for graphics processing units enables genome-wide testing of epistasis in sporadic ALS"],"prefix":"10.1093","volume":"26","author":[{"given":"Casey S.","family":"Greene","sequence":"first","affiliation":[{"name":"1 Department of Genetics and 2 Department of Pathology, Dartmouth Medical School, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas A.","family":"Sinnott-Armstrong","sequence":"additional","affiliation":[{"name":"1 Department of Genetics and 2 Department of Pathology, Dartmouth Medical School, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel S.","family":"Himmelstein","sequence":"additional","affiliation":[{"name":"1 Department of Genetics and 2 Department of Pathology, Dartmouth Medical School, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Park","sequence":"additional","affiliation":[{"name":"1 Department of Genetics and 2 Department of Pathology, Dartmouth Medical School, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason H.","family":"Moore","sequence":"additional","affiliation":[{"name":"1 Department of Genetics and 2 Department of Pathology, Dartmouth Medical School, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent T.","family":"Harris","sequence":"additional","affiliation":[{"name":"1 Department of Genetics and 2 Department of Pathology, Dartmouth Medical School, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,1,16]]},"reference":[{"key":"2023012511010595200_B1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","article-title":"Haploview: analysis and visualization of LD and haplotype maps","volume":"21","author":"Barrett","year":"2005","journal-title":"Bioinformatics"},{"key":"2023012511010595200_B2","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1093\/hmg\/ddm361","article-title":"A genome-wide association study of sporadic ALS in a homogenous irish population","volume":"17","author":"Cronin","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"2023012511010595200_B3","doi-asserted-by":"crossref","first-page":"e5639","DOI":"10.1371\/journal.pone.0005639","article-title":"Failure to replicate a genetic association may provide important clues about genetic architecture","volume":"4","author":"Greene","year":"2009","journal-title":"PLoS ONE"},{"key":"2023012511010595200_B4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrg1521","article-title":"Genome-wide association studies for common diseases and complex traits","volume":"6","author":"Hirschhorn","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"2023012511010595200_B5","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1086\/321276","article-title":"Multifactor dimensionality reduction reveals high-order interactions among estrogen metabolism genes in sporadic breast cancer","volume":"69","author":"Ritchie","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"2023012511010595200_B6","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S1474-4422(07)70037-6","article-title":"Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data","volume":"6","author":"Schymick","year":"2007","journal-title":"Lancet Neurol."},{"key":"2023012511010595200_B7","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1126\/science.316.5833.1840c","article-title":"Problems with genome-wide association studies","volume":"316","author":"Shriner","year":"2007","journal-title":"Science"},{"key":"2023012511010595200_B8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/1756-0500-2-149","article-title":"Accelerating epistasis analysis in human genetics with consumer graphics hardware","volume":"2","author":"Sinnott-Armstrong","year":"2009","journal-title":"BMC Res. Notes"},{"key":"2023012511010595200_B9","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrg1522","article-title":"Genome-wide association studies: theoretical and practical concerns","volume":"6","author":"Wang","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"2023012511010595200_B10","first-page":"1841","article-title":"Problems with genome-wide association studies","volume":"316","author":"Williams","year":"2007","journal-title":"Science"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/5\/694\/48860700\/bioinformatics_26_5_694.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/5\/694\/48860700\/bioinformatics_26_5_694.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T11:06:38Z","timestamp":1674644798000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/26\/5\/694\/212616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,1,16]]},"references-count":10,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btq009","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,3,1]]},"published":{"date-parts":[[2010,1,16]]}}}