{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T13:24:57Z","timestamp":1743427497727,"version":"3.37.3"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Intramural Research Program of the National Institutes of Health","award":["ES040007"],"award-info":[{"award-number":["ES040007"]}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["ES040007"],"award-info":[{"award-number":["ES040007"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Epistasis may play an etiologic role in complex diseases, but research has been hindered because identification of interactions among sets of single nucleotide polymorphisms (SNPs) requires exploration of immense search spaces. Current approaches using nuclear families accommodate at most several hundred candidate SNPs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>GADGETS detects epistatic SNP-sets by applying a genetic algorithm to case-parent or case-sibling data. To allow for multiple epistatic sets, island subpopulations of SNP-sets evolve separately under selection for evident joint relevance to disease risk. The software evaluates the identified SNP-sets via permutation testing and provides graphical visualization. GADGETS correctly identified epistatic SNP-sets in realistically simulated case-parent triads with 10\u2009000 candidate SNPs, far more SNPs than competitors can handle, and it outperformed competitors in simulations with many fewer SNPs. Applying GADGETS to family-based oral-clefting data from dbGaP identified SNP-sets with possible epistatic effects on risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>GADGETS is part of the epistasisGA package at https:\/\/github.com\/mnodzenski\/epistasisGA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab766","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T12:23:59Z","timestamp":1636115039000},"page":"1052-1058","source":"Crossref","is-referenced-by-count":2,"title":["GADGETS: a genetic algorithm for detecting epistasis using nuclear families"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5476-8427","authenticated-orcid":false,"given":"Michael","family":"Nodzenski","sequence":"first","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-5307","authenticated-orcid":false,"given":"Min","family":"Shi","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709, USA"}]},{"given":"Juno M","family":"Krahn","sequence":"additional","affiliation":[{"name":"Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709, USA"}]},{"given":"Alison S","family":"Wise","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709, USA"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4208-0259","authenticated-orcid":false,"given":"Leping","family":"Li","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7142-2812","authenticated-orcid":false,"given":"David M","family":"Umbach","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709, USA"}]},{"given":"Clarice R","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, NIH , Research Triangle Park, NC 27709, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"2024031409164384400_btab766-B1","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/hdy.2014.4","article-title":"Cuckoo search epistasis: a new method for exploring significant genetic interactions","volume":"112","author":"Aflakparast","year":"2014","journal-title":"Heredity"},{"key":"2024031409164384400_btab766-B2","first-page":"16","volume-title":"Advances in Genetic Programming","author":"Andre","year":"1996"},{"key":"2024031409164384400_btab766-B3","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/ng.580","article-title":"A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4","volume":"42","author":"Beaty","year":"2010","journal-title":"Nat. Genet"},{"key":"2024031409164384400_btab766-B4","doi-asserted-by":"crossref","first-page":"e10304","DOI":"10.1371\/journal.pone.0010304","article-title":"FAM-MDR: a flexible family-based multifactor dimensionality reduction technique to detect epistasis using related individuals","volume":"5","author":"Cattaert","year":"2010","journal-title":"PLoS One"},{"key":"2024031409164384400_btab766-B5","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00439-013-1361-9","article-title":"A unified GMDR method for detecting gene-gene interactions in family and unrelated samples with application to nicotine dependence","volume":"133","author":"Chen","year":"2014","journal-title":"Hum. Genet"},{"key":"2024031409164384400_btab766-B6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1086\/338007","article-title":"A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case\/control or family data: application to HLA in type 1 diabetes","volume":"70","author":"Cordell","year":"2002","journal-title":"Am. J. Hum. Genet"},{"key":"2024031409164384400_btab766-B7","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/gepi.21602","article-title":"SVM-based generalized multifactor dimensionality reduction approaches for detecting gene-gene interactions in family studies","volume":"36","author":"Fang","year":"2012","journal-title":"Genet. Epidemiol"},{"volume-title":"Adaptation in Natural and Artificial Systems","year":"1975","author":"Holland","key":"2024031409164384400_btab766-B8"},{"key":"2024031409164384400_btab766-B9","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1093\/bioinformatics\/btu702","article-title":"MACOED: a multi-objective ant colony optimization algorithm for SNP epistasis detection in genome-wide association studies","volume":"31","author":"Jing","year":"2015","journal-title":"Bioinformatics"},{"key":"2024031409164384400_btab766-B10","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/gepi.20488","article-title":"Detection of SNP-SNP interactions in trios of parents with schizophrenic children","volume":"34","author":"Li","year":"2010","journal-title":"Genet. Epidemiol"},{"key":"2024031409164384400_btab766-B11","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/gepi.21888","article-title":"Gene-gene interaction among WNT genes for oral cleft in trios","volume":"39","author":"Li","year":"2015","journal-title":"Genet. Epidemiol"},{"key":"2024031409164384400_btab766-B12","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.ygeno.2018.07.014","article-title":"TrioMDR: detecting SNP interactions in trio families with model-based multifactor dimensionality reduction","volume":"111","author":"Liu","year":"2019","journal-title":"Genomics"},{"key":"2024031409164384400_btab766-B13","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ajhg.2008.09.001","article-title":"A combinatorial approach to detecting gene-gene and gene-environment interactions in family studies","volume":"83","author":"Lou","year":"2008","journal-title":"Am. J. Hum. Genet"},{"key":"2024031409164384400_btab766-B14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/gepi.20128","article-title":"A novel method to identify gene-gene effects in nuclear families: the MDR-PDT","volume":"30","author":"Martin","year":"2006","journal-title":"Genet. Epidemiol"},{"key":"2024031409164384400_btab766-B15","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2202\/1544-6115.1585","article-title":"Permutation P-values should never be zero: calculating exact P-values when permutations are randomly drawn","volume":"9","author":"Phipson","year":"2010","journal-title":"Stat. Appl. Genet. Mol. Biol"},{"key":"2024031409164384400_btab766-B16","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/sim.4780130206","article-title":"Non-hierarchical logistic models and case-only designs for assessing susceptibility in population-based case-control studies","volume":"13","author":"Piegorsch","year":"1994","journal-title":"Stat. Med"},{"key":"2024031409164384400_btab766-B17","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet"},{"key":"2024031409164384400_btab766-B18","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":"2024031409164384400_btab766-B19","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1469-1809.2010.00623.x","article-title":"Importance measures for epistatic interactions in case-parent trios","volume":"75","author":"Schwender","year":"2011","journal-title":"Ann. Hum. Genet"},{"key":"2024031409164384400_btab766-B20","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1097\/EDE.0b013e31822ffbe7","article-title":"How much are we missing in SNP-by-SNP analyses of genome wide association studies?","volume":"22","author":"Shi","year":"2011","journal-title":"Epidemiology"},{"key":"2024031409164384400_btab766-B21","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12859-017-2004-2","article-title":"Simulating autosomal genotypes with realistic linkage disequilibrium and a spiked-in genetic effect","volume":"19","author":"Shi","year":"2018","journal-title":"BMC Bioinform"},{"key":"2024031409164384400_btab766-B22","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1136\/bmj.39458.563611.AE","article-title":"Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives","volume":"336","author":"Sivertsen","year":"2008","journal-title":"BMJ"},{"key":"2024031409164384400_btab766-B23","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1093\/bioinformatics\/btw077","article-title":"An efficient gene-gene interaction test for genome-wide association studies in trio families","volume":"32","author":"Sung","year":"2016","journal-title":"Bioinformatics"},{"key":"2024031409164384400_btab766-B24","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1756-0500-3-117","article-title":"AntEpiSeeker: detecting epistatic interactions for case control studies using a two-stage ant colony optimization algorithm","volume":"3","author":"Wang","year":"2010","journal-title":"BMC Res. Notes"},{"key":"2024031409164384400_btab766-B25","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/gepi.22342","article-title":"Exploring gene-gene interaction in family-based data with an unsupervised machine learning method: EPISFA","volume":"44","author":"Xiang","year":"2020","journal-title":"Genet. Epidemiol"},{"key":"2024031409164384400_btab766-B26","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1093\/bioinformatics\/btn652","article-title":"SNPHarvester: a filtering-based approach for detecting epistatic interactions in genome-wide association studies","volume":"25","author":"Yang","year":"2009","journal-title":"Bioinformatics"},{"key":"2024031409164384400_btab766-B27","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/ng2110","article-title":"Bayesian inference of epistatic interactions in case-control studies","volume":"39","author":"Zhang","year":"2007","journal-title":"Nat. Genet"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btab766\/41905482\/btab766.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/38\/4\/1052\/56967665\/btab766.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/38\/4\/1052\/56967665\/btab766.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T09:17:17Z","timestamp":1710407837000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/38\/4\/1052\/6426075"}},"subtitle":[],"editor":[{"given":"Russell","family":"Schwartz","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2021,11,12]]},"references-count":27,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,1,27]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btab766","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"type":"print","value":"1367-4803"},{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2022,2,15]]},"published":{"date-parts":[[2021,11,12]]}}}