{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T14:14:18Z","timestamp":1778336058043,"version":"3.51.4"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T00:00:00Z","timestamp":1515715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U01 DK085524, U01 DK085584, U01 DK085501, U01 DK085526 and U01 DK085545"],"award-info":[{"award-number":["U01 DK085524, U01 DK085584, U01 DK085501, U01 DK085526 and U01 DK085545"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["076113 and 085475"],"award-info":[{"award-number":["076113 and 085475"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Epistasis provides a feasible way for probing potential genetic mechanism of complex traits. However, time-consuming computation challenges successful detection of interaction in practice, especially when linear mixed model (LMM) is used to control type I error in the presence of population structure and cryptic relatedness.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A rapid epistatic mixed-model association analysis (REMMA) method was developed to overcome computational limitation. This method first estimates individuals\u2019 epistatic effects by an extended genomic best linear unbiased prediction (EG-BLUP) model with additive and epistatic kinship matrix, then pairwise interaction effects are obtained by linear retransformations of individuals\u2019 epistatic effects. Simulation studies showed that REMMA could control type I error and increase statistical power in detecting epistatic QTNs in comparison with existing LMM-based FaST-LMM. We applied REMMA to two real datasets, a mouse dataset and the Wellcome Trust Case Control Consortium (WTCCC) data. Application to the mouse data further confirmed the performance of REMMA in controlling type I error. For the WTCCC data, we found most epistatic QTNs for type 1 diabetes (T1D) located in a major histocompatibility complex (MHC) region, from which a large interacting network with 12 hub genes (interacting with ten or more genes) was established.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Our REMMA method can be freely accessed at https:\/\/github.com\/chaoning\/REMMA.<\/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\/bty017","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T12:35:06Z","timestamp":1515587706000},"page":"1817-1825","source":"Crossref","is-referenced-by-count":32,"title":["A rapid epistatic mixed-model association analysis by linear retransformations of genomic estimated values"],"prefix":"10.1093","volume":"34","author":[{"given":"Chao","family":"Ning","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimin","family":"Kang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Mrode","sequence":"additional","affiliation":[{"name":"Animal Biosciences, International Livestock Institute, Nairobi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shizhong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Botany and Plant Science, University of California, Riverside, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,1,12]]},"reference":[{"key":"2023012713533487400_bty017-B1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/1753-6561-8-S1-S1","article-title":"Genetic Analysis Workshop 18: methods and strategies for analyzing human sequence and phenotype data in members of extended pedigrees","volume":"8","author":"Bickeboller","year":"2014","journal-title":"BMC Proc"},{"key":"2023012713533487400_bty017-B2","doi-asserted-by":"crossref","first-page":"8712","DOI":"10.1038\/ncomms9712","article-title":"Genetic interactions contribute less than additive effects to quantitative trait variation in yeast","volume":"6","author":"Bloom","year":"2015","journal-title":"Nat. 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