{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:19:42Z","timestamp":1773814782035,"version":"3.50.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"S9","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Because common complex diseases are affected by multiple genes and environmental factors, it is essential to investigate gene-gene and\/or gene-environment interactions to understand genetic architecture of complex diseases. After the great success of large scale genome-wide association (GWA) studies using the high density single nucleotide polymorphism (SNP) chips, the study of gene-gene interaction becomes a next challenge. Multifactor dimensionality reduction (MDR) analysis has been widely used for the gene-gene interaction analysis. In practice, however, it is not easy to perform high order gene-gene interaction analyses via MDR in genome-wide level because it requires exploring a huge search space and suffers from a computational burden due to high dimensionality.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We propose dimensional reduction analysis, Gene-MDR analysis for the fast and efficient high order gene-gene interaction analysis. The proposed Gene-MDR method is composed of two-step applications of MDR: within- and between-gene MDR analyses. First, within-gene MDR analysis summarizes each gene effect via MDR analysis by combining multiple SNPs from the same gene. Second, between-gene MDR analysis then performs interaction analysis using the summarized gene effects from within-gene MDR analysis. We apply the Gene-MDR method to bipolar disorder (BD) GWA data from Wellcome Trust Case Control Consortium (WTCCC). The results demonstrate that Gene-MDR is capable of detecting high order gene-gene interactions associated with BD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>By reducing the dimension of genome-wide data from SNP level to gene level, Gene-MDR efficiently identifies high order gene-gene interactions. Therefore, Gene-MDR can provide the key to understand complex disease etiology.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-13-s9-s5","type":"journal-article","created":{"date-parts":[[2012,12,5]],"date-time":"2012-12-05T22:17:10Z","timestamp":1354745830000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["A novel method to identify high order gene-gene interactions in genome-wide association studies: Gene-based MDR"],"prefix":"10.1186","volume":"13","author":[{"given":"Sohee","family":"Oh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaehoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Seok","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Weir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyooseob","family":"Ha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taesung","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,6,11]]},"reference":[{"key":"5197_CR1","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1126\/science.1109557","volume":"308","author":"RJ Klein","year":"2005","unstructured":"Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J: Complement factor H polymorphism in age-related macular degeneration. 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