{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:53:57Z","timestamp":1780484037971,"version":"3.54.1"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"S2","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2018,3]]},"DOI":"10.1186\/s12918-018-0543-4","type":"journal-article","created":{"date-parts":[[2018,11,22]],"date-time":"2018-11-22T10:55:06Z","timestamp":1542884106000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["GxGrare: gene-gene interaction analysis method for rare variants from high-throughput sequencing data"],"prefix":"10.1186","volume":"12","author":[{"given":"Minseok","family":"Kwon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangseob","family":"Leem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taesung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,3,19]]},"reference":[{"issue":"7261","key":"543_CR1","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1136\/bmj.321.7261.624","volume":"321","author":"K McPherson","year":"2000","unstructured":"McPherson K, Steel C, Dixon J. Breast cancer-epidemiology, risk factors, and genetics. BMJ: British Medical Journal. 2000;321(7261):624.","journal-title":"BMJ: British Medical Journal"},{"issue":"9","key":"543_CR2","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/S0168-9525(01)02410-6","volume":"17","author":"DE Reich","year":"2001","unstructured":"Reich DE, Lander ES. On the allelic spectrum of human disease. Trends Genet. 2001;17(9):502\u201310.","journal-title":"Trends Genet"},{"key":"543_CR3","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/nature08494","volume":"461","author":"T Manolio","year":"2009","unstructured":"Manolio T, Collins F, Cox N, Goldstein D, Hindorff L, Hunter D, McCarthy M, Ramos E, Cardon L, Chakravarti A. Finding the missing heritability of complex diseases. Nature. 2009;461:747\u201353.","journal-title":"Nature"},{"issue":"12","key":"543_CR4","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/ng.717","volume":"42","author":"A Franke","year":"2010","unstructured":"Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, Lees CW, Balschun T, Lee J, Roberts R. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet. 2010;42(12):1118\u201325.","journal-title":"Nat Genet"},{"issue":"1","key":"543_CR5","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1086\/321272","volume":"69","author":"JK Pritchard","year":"2001","unstructured":"Pritchard JK. Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet. 2001;69(1):124\u201337.","journal-title":"Am J Hum Genet"},{"issue":"Suppl 1","key":"543_CR6","doi-asserted-by":"publisher","first-page":"S62","DOI":"10.2337\/dc09-S062","volume":"32","author":"A American Diabetes","year":"2009","unstructured":"American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009;32(Suppl 1):S62\u20137.","journal-title":"Diabetes Care"},{"issue":"3","key":"543_CR7","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.ajhg.2008.06.024","volume":"83","author":"B Li","year":"2008","unstructured":"Li B, Leal SM. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am J Hum Genet. 2008;83(3):311\u201321.","journal-title":"Am J Hum Genet"},{"issue":"2","key":"543_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000384","volume":"5","author":"BE Madsen","year":"2009","unstructured":"Madsen BE, Browning SR. A groupwise association test for rare mutations using a weighted sum statistic. PLoS Genet. 2009;5(2):e1000384.","journal-title":"PLoS Genet"},{"issue":"6","key":"543_CR9","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.ajhg.2010.04.005","volume":"86","author":"AL Price","year":"2010","unstructured":"Price AL, Kryukov GV, de Bakker PI, Purcell SM, Staples J, Wei L-J, Sunyaev SR. Pooled association tests for rare variants in exon-resequencing studies. Am J Hum Genet. 2010;86(6):832\u20138.","journal-title":"Am J Hum Genet"},{"issue":"2","key":"543_CR10","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1002\/gepi.20450","volume":"34","author":"AP Morris","year":"2010","unstructured":"Morris AP, Zeggini E. An evaluation of statistical approaches to rare variant analysis in genetic association studies. Genet Epidemiol. 2010;34(2):188\u201393.","journal-title":"Genet Epidemiol"},{"issue":"10","key":"543_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001156","volume":"6","author":"DJ Liu","year":"2010","unstructured":"Liu DJ, Leal SM. A novel adaptive method for the analysis of next-generation sequencing data to detect complex trait associations with rare variants due to gene main effects and interactions. PLoS Genet. 2010;6(10):e1001156.","journal-title":"PLoS Genet"},{"issue":"1","key":"543_CR12","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.ajhg.2011.05.029","volume":"89","author":"MC Wu","year":"2011","unstructured":"Wu MC, Lee S, Cai T, Li Y, Boehnke M, Lin X. Rare-variant association testing for sequencing data with the sequence kernel association test. Am J Hum Genet. 2011;89(1):82\u201393.","journal-title":"Am J Hum Genet"},{"issue":"2","key":"543_CR13","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.ajhg.2012.06.007","volume":"91","author":"S Lee","year":"2012","unstructured":"Lee S, Emond MJ, Bamshad MJ, Barnes KC, Rieder MJ, Nickerson DA, Team ELP, Christiani DC, Wurfel MM, Lin X. Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies. Am J Hum Genet. 2012;91(2):224\u201337.","journal-title":"Am J Hum Genet"},{"issue":"6","key":"543_CR14","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/j.ajhg.2012.04.010","volume":"90","author":"I Ionita-Laza","year":"2012","unstructured":"Ionita-Laza I, Makarov V, Buxbaum JD, Consortium AAS. Scan-statistic approach identifies clusters of rare disease variants in LRP2, a gene linked and associated with autism spectrum disorders, in three datasets. Am J Hum Genet. 2012;90(6):1002\u201313.","journal-title":"Am J Hum Genet"},{"issue":"11","key":"543_CR15","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1007\/s00439-013-1335-y","volume":"132","author":"DJ Schaid","year":"2013","unstructured":"Schaid DJ, Sinnwell JP, McDonnell SK, Thibodeau SN. Detecting genomic clustering of risk variants from sequence data: cases versus controls. Hum Genet. 2013;132(11):1301\u20139.","journal-title":"Hum Genet"},{"issue":"4","key":"543_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094337","volume":"9","author":"W-Y Lin","year":"2014","unstructured":"Lin W-Y. Association testing of clustered rare causal variants in case-control studies. PLoS One. 2014;9(4):e94337.","journal-title":"PLoS One"},{"issue":"1","key":"543_CR17","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1086\/321276","volume":"69","author":"MD Ritchie","year":"2001","unstructured":"Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet. 2001;69(1):138\u201347.","journal-title":"Am J Hum Genet"},{"issue":"1","key":"543_CR18","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1093\/bioinformatics\/btl557","volume":"23","author":"Y Chung","year":"2007","unstructured":"Chung Y, Lee SY, Elston RC, Park T. Odds ratio based multifactor-dimensionality reduction method for detecting gene-gene interactions. Bioinformatics. 2007;23(1):71\u20136.","journal-title":"Bioinformatics"},{"issue":"19","key":"543_CR19","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.1093\/bioinformatics\/btm396","volume":"23","author":"SY Lee","year":"2007","unstructured":"Lee SY, Chung Y, Elston RC, Kim Y, Park T. Log-linear model-based multifactor dimensionality reduction method to detect gene\u2013gene interactions. Bioinformatics. 2007;23(19):2589\u201395.","journal-title":"Bioinformatics"},{"issue":"9","key":"543_CR20","first-page":"1","volume":"13","author":"S Oh","year":"2012","unstructured":"Oh S, Lee J, Kwon M-S, Weir B, Ha K, Park T. A novel method to identify high order gene-gene interactions in genome-wide association studies: gene-based MDR. BMC bioinformatics. 2012;13(9):1.","journal-title":"BMC bioinformatics"},{"issue":"Suppl 1","key":"543_CR21","first-page":"S6","volume":"7","author":"M-S Kwon","year":"2014","unstructured":"Kwon M-S, Park M, Park T. IGENT: efficient entropy based algorithm for genome-wide gene-gene interaction analysis. BMC Med Genet. 2014;7(Suppl 1):S6.","journal-title":"BMC Med Genet"},{"issue":"6","key":"543_CR22","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1086\/518312","volume":"80","author":"X-Y Lou","year":"2007","unstructured":"Lou X-Y, Chen G-B, Yan L, Ma JZ, Zhu J, Elston RC, Li MD. A generalized combinatorial approach for detecting Gene-by-gene and gene-by-environment interactions with application to nicotine dependence. Am J Hum Genet. 2007;80(6):1125\u201337.","journal-title":"Am J Hum Genet"},{"issue":"12","key":"543_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083057","volume":"8","author":"R Fan","year":"2013","unstructured":"Fan R, Lo S-H. A robust model-free approach for rare variants association studies incorporating gene-gene and gene-environmental interactions. PLoS One. 2013;8(12):e83057.","journal-title":"PLoS One"},{"issue":"2","key":"543_CR24","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/nrg3118","volume":"13","author":"G Gibson","year":"2012","unstructured":"Gibson G. Rare and common variants: twenty arguments. Nat Rev Genet. 2012;13(2):135\u201345.","journal-title":"Nat Rev Genet"},{"issue":"2","key":"543_CR25","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","volume":"6","author":"P Cingolani","year":"2012","unstructured":"Cingolani P, Platts A, Wang LL, Coon M, Nguyen T, Wang L, Land SJ, Lu X, Ruden DM. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila Melanogaster strain w1118; iso-2; iso-3. Fly. 2012;6(2):80\u201392.","journal-title":"Fly"},{"issue":"20","key":"543_CR26","first-page":"21","volume":"7","author":"I Adzhubei","year":"2013","unstructured":"Adzhubei I, Jordan DM, Sunyaev SR. Predicting functional effect of human missense mutations using PolyPhen-2. Current protocols in human genetics. 2013;7(20):21\u20137. 20. 41","journal-title":"Current protocols in human genetics"},{"issue":"W1","key":"543_CR27","doi-asserted-by":"publisher","first-page":"W452","DOI":"10.1093\/nar\/gks539","volume":"40","author":"N-L Sim","year":"2012","unstructured":"Sim N-L, Kumar P, Hu J, Henikoff S, Schneider G, Ng PC. SIFT web server: predicting effects of amino acid substitutions on proteins. Nucleic Acids Res. 2012;40(W1):W452\u20137.","journal-title":"Nucleic Acids Res"},{"issue":"8","key":"543_CR28","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1101\/gr.3715005","volume":"15","author":"A Siepel","year":"2005","unstructured":"Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 2005;15(8):1034\u201350.","journal-title":"Genome Res"},{"issue":"13","key":"543_CR29","doi-asserted-by":"publisher","first-page":"i266","DOI":"10.1093\/bioinformatics\/btr241","volume":"27","author":"J Sadri","year":"2011","unstructured":"Sadri J, Diallo AB, Blanchette M. Predicting site-specific human selective pressure using evolutionary signatures. Bioinformatics. 2011;27(13):i266\u201374.","journal-title":"Bioinformatics"},{"issue":"4","key":"543_CR30","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1002\/gepi.20211","volume":"31","author":"DR Velez","year":"2007","unstructured":"Velez DR, White BC, Motsinger AA, Bush WS, Ritchie MD, Williams SM, Moore JH. A balanced accuracy function for epistasis modeling in imbalanced datasets using multifactor dimensionality reduction. Genet Epidemiol. 2007;31(4):306\u201315.","journal-title":"Genet Epidemiol"},{"key":"543_CR31","doi-asserted-by":"crossref","unstructured":"Goebel B, Dawy Z, Hagenauer J, Mueller JC: An approximation to the distribution of finite sample size mutual information estimates. In: Communications, 2005 ICC 2005 2005 IEEE International Conference on: 16\u201320 May 2005 2005; 2005: 1102\u20131106 Vol. 1102.","DOI":"10.1109\/ICC.2005.1494518"},{"key":"543_CR32","doi-asserted-by":"crossref","unstructured":"Kwon M-S, Kim K, Lee S, Chung W, Yi S-G, Namkung J, Park T. GWAS-GMDR: a program package for genome-wide scan of gene-gene interactions with covariate adjustment based on multifactor dimensionality reduction. In: bioinformatics and biomedicine workshops (BIBMW), 2011 IEEE international conference on: 2011. IEEE. 2011:703\u20137.","DOI":"10.1109\/BIBMW.2011.6112456"},{"issue":"4","key":"543_CR33","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/ng1537","volume":"37","author":"J Marchini","year":"2005","unstructured":"Marchini J, Donnelly P, Cardon LR. Genome-wide strategies for detecting multiple loci that influence complex diseases. Nat Genet. 2005;37(4):413\u20137.","journal-title":"Nat Genet"},{"issue":"1","key":"543_CR34","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1186\/1471-2105-9-238","volume":"9","author":"WS Bush","year":"2008","unstructured":"Bush WS, Edwards TL, Dudek SM, McKinney BA, Ritchie MD. Alternative contingency table measures improve the power and detection of multifactor dimensionality reduction. Bmc Bioinformatics. 2008;9(1):238.","journal-title":"Bmc Bioinformatics"},{"issue":"3","key":"543_CR35","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1093\/bioinformatics\/btn629","volume":"25","author":"J Namkung","year":"2009","unstructured":"Namkung J, Kim K, Yi S, Chung W, Kwon M-S, Park T. New evaluation measures for multifactor dimensionality reduction classifiers in gene\u2013gene interaction analysis. Bioinformatics. 2009;25(3):338\u201345.","journal-title":"Bioinformatics"},{"key":"543_CR36","doi-asserted-by":"crossref","unstructured":"Khomula EV, Borisyuk AL, Viatchenko-Karpinski VY, Briede A, Belan PV, Voitenko NV. Nociceptive neurons differentially express fast and slow T-type Ca2. Neural plasticity. 2014;2014","DOI":"10.1155\/2014\/938235"},{"issue":"24","key":"543_CR37","doi-asserted-by":"publisher","first-page":"21405","DOI":"10.1074\/jbc.M102488200","volume":"276","author":"L Wang","year":"2001","unstructured":"Wang L, Guo Y, Huang W-J, Ke X, Poyet J-L, Manji GA, Merriam S, Glucksmann MA, DiStefano PS, Alnemri ES. Card10 is a novel caspase recruitment domain\/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-\u03baB. J Biol Chem. 2001;276(24):21405\u20139.","journal-title":"J Biol Chem"},{"issue":"4","key":"543_CR38","first-page":"521","volume":"21","author":"K Strait","year":"2008","unstructured":"Strait K, Li Y, Dillehay DL, Weitzmann MN. Suppression of NF-kappa B activation blocks osteoclastic bone resorption during estrogen deficiency. Int J Mol Med. 2008;21(4):521.","journal-title":"Int J Mol Med"},{"key":"543_CR39","unstructured":"Peters M: Ranking Genome Wide Association Data by fusing Genomic and Functional Information."},{"issue":"24","key":"543_CR40","doi-asserted-by":"publisher","first-page":"17859","DOI":"10.1074\/jbc.M112.440677","volume":"288","author":"PN Silva","year":"2013","unstructured":"Silva PN, Altamentova SM, Kilkenny DM, Rocheleau JV. Fibroblast growth factor receptor like-1 (FGFRL1) interacts with SHP-1 phosphatase at insulin secretory granules and induces beta-cell ERK1\/2 protein activation. J Biol Chem. 2013;288(24):17859\u201370.","journal-title":"J Biol Chem"},{"issue":"2","key":"543_CR41","doi-asserted-by":"publisher","first-page":"351","DOI":"10.9734\/BJMMR\/2013\/2614","volume":"3","author":"ME Hern\u00e1ndez-Caballero","year":"2013","unstructured":"Hern\u00e1ndez-Caballero ME, Arenas-Aranda DJ, Ch\u00e1vez-Torres R, Sierra-Ram\u00edrez JA, Calzada-Mendoza CC. Impact of D-bifunctional protein deficiency on telomere length and gene expression in a child. British Journal of Medicine and Medical Research. 2013;3(2):351.","journal-title":"British Journal of Medicine and Medical Research"},{"issue":"1","key":"543_CR42","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.cmet.2007.11.009","volume":"7","author":"D Speidel","year":"2008","unstructured":"Speidel D, Salehi A, Obermueller S, Lundquist I, Brose N, Renstr\u00f6m E, Rorsman P. CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic \u03b2 cells. Cell Metab. 2008;7(1):57\u201367.","journal-title":"Cell Metab"},{"issue":"12","key":"543_CR43","doi-asserted-by":"publisher","first-page":"4210","DOI":"10.1073\/pnas.0307349101","volume":"101","author":"K Del Villar","year":"2004","unstructured":"Del Villar K, Miller CA. Down-regulation of DENN\/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer's disease brain and hippocampal neurons. Proc Natl Acad Sci. 2004;101(12):4210\u20135.","journal-title":"Proc Natl Acad Sci"},{"issue":"5","key":"543_CR44","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.2337\/db13-0707","volume":"63","author":"L-c Li","year":"2014","unstructured":"Li L-c, Wang Y, Carr R, Haddad CS, Li Z, Qian L, Oberholzer J, Maker AV, Wang Q, Prabhakar BS. IG20\/MADD plays a critical role in glucose-induced insulin secretion. Diabetes. 2014;63(5):1612\u201323.","journal-title":"Diabetes"},{"issue":"4","key":"543_CR45","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.clon.2010.02.001","volume":"22","author":"L Healy","year":"2010","unstructured":"Healy L, Ryan A, Carroll P, Ennis D, Crowley V, Boyle T, Kennedy M, Connolly E, Reynolds J. Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer. Clin Oncol. 2010;22(4):281\u20138.","journal-title":"Clin Oncol"},{"issue":"5","key":"543_CR46","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1093\/dnares\/11.5.315","volume":"11","author":"M Nishimura","year":"2004","unstructured":"Nishimura M, Yokoi N, Miki T, Horikawa Y, Yoshioka H, Takeda J, Ohara O, Seino S. Construction of a multi-functional cDNA library specific for mouse pancreatic islets and its application to microarray. DNA Res. 2004;11(5):315\u201323.","journal-title":"DNA Res"},{"issue":"1","key":"543_CR47","doi-asserted-by":"publisher","first-page":"E78","DOI":"10.1152\/ajpendo.00542.2012","volume":"305","author":"DD McCoy","year":"2013","unstructured":"McCoy DD, Zhou L, Nguyen A-K, Watts AG, Donovan CM, McKemy DD. Enhanced insulin clearance in mice lacking TRPM8 channels. Am J Physiol-Endocrinology and Metabolism. 2013;305(1):E78\u201388.","journal-title":"Am J Physiol-Endocrinology and Metabolism"},{"issue":"2","key":"543_CR48","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1093\/jmcb\/mjs001","volume":"4","author":"S Ma","year":"2012","unstructured":"Ma S, Yu H, Zhao Z, Luo Z, Chen J, Ni Y, Jin R, Ma L, Wang P, Zhu Z. Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity. J Mol Cell Biol. 2012;4(2):88\u201396.","journal-title":"J Mol Cell Biol"},{"issue":"12","key":"543_CR49","doi-asserted-by":"publisher","first-page":"2670","DOI":"10.1093\/carcin\/bgu193","volume":"35","author":"JW Hoskins","year":"2014","unstructured":"Hoskins JW, Jia J, Flandez M, Parikh H, Xiao W, Collins I, Emmanuel MA, Ibrahim A, Powell J, Zhang L. Transcriptome analysis of pancreatic cancer reveals a tumor suppressor function for HNF1A. Carcinogenesis. 2014;35(12):2670\u20138.","journal-title":"Carcinogenesis"},{"issue":"6","key":"543_CR50","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1056\/NEJMoa1400382","volume":"371","author":"AC Antoniou","year":"2014","unstructured":"Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylk\u00e4s K, Roberts J, Lee A, Subramanian D, De Leeneer K, Fostira F. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371(6):497\u2013506.","journal-title":"N Engl J Med"},{"issue":"3","key":"543_CR51","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1097\/MPA.0b013e318209e05d","volume":"40","author":"JT Magruder","year":"2011","unstructured":"Magruder JT, Elahi D, Andersen DK. Diabetes and pancreatic cancer: chicken or egg? Pancreas. 2011;40(3):339\u201351.","journal-title":"Pancreas"},{"issue":"6","key":"543_CR52","doi-asserted-by":"publisher","first-page":"4414","DOI":"10.1128\/MCB.19.6.4414","volume":"19","author":"S Kishida","year":"1999","unstructured":"Kishida S, Yamamoto H, Hino S-i, Ikeda S, Kishida M, Kikuchi A. DIX domains of Dvl and Axin are necessary for protein interactions and their ability to regulate \u03b2-catenin stability. Mol Cell Biol. 1999;19(6):4414\u201322.","journal-title":"Mol Cell Biol"},{"issue":"10","key":"543_CR53","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1182\/blood.V91.10.3593","volume":"91","author":"R Kozyraki","year":"1998","unstructured":"Kozyraki R, Kristiansen M, Silahtaroglu A, Hansen C, Jacobsen C, Tommerup N, Verroust PJ, Moestrup SK. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region. Blood. 1998;91(10):3593\u2013600.","journal-title":"Blood"},{"key":"543_CR54","unstructured":"Acton A: Diabetes: New Insights for the Healthcare Professional: 2012 Edition. ScholarlyEditions 2012."}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12918-018-0543-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12918-018-0543-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12918-018-0543-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T05:08:04Z","timestamp":1775279284000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/s12918-018-0543-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3]]},"references-count":54,"journal-issue":{"issue":"S2","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["543"],"URL":"https:\/\/doi.org\/10.1186\/s12918-018-0543-4","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3]]},"assertion":[{"value":"19 March 2018","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"KARE is are a part of Korean Genome Epidemiology Study (KoGES). In this study, the exome sequencing data from 1037 samples of KARE study were used. KARE dataset was used under the partnership of T2D-GENES. The study using KARE samples was approved by two institutional review boards at Seoul National University and the National Institute of Health, Korea.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All participants of KARE were provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"19"}}