title: Identification of epistatic interactions through genome-wide association studies in sporadic medullary and juvenile papillary thyroid carcinomas.
abstract: BACKGROUND
  The molecular mechanisms leading to sporadic medullary thyroid carcinoma (sMTC) and juvenile papillary thyroid carcinoma (PTC), two rare tumours of the thyroid gland, remain poorly understood. Genetic studies on thyroid carcinomas have been conducted, although just a few loci have been systematically associated. Given the difficulties to obtain single-loci associations, this work expands its scope to the study of epistatic interactions that could help to understand the genetic architecture of complex diseases and explain new heritable components of genetic risk.
  
  
  METHODS
  We carried out the first screening for epistasis by Multifactor-Dimensionality Reduction (MDR) in genome-wide association study (GWAS) on sMTC and juvenile PTC, to identify the potential simultaneous involvement of pairs of variants in the disease.
  
  
  RESULTS
  We have identified two significant epistatic gene interactions in sMTC (CHFR-AC016582.2 and C8orf37-RNU1-55P) and three in juvenile PTC (RP11-648k4.2-DIO1, RP11-648k4.2-DMGDH and RP11-648k4.2-LOXL1). Interestingly, each interacting gene pair included a non-coding RNA, providing thus support to the relevance that these elements are increasingly gaining to explain carcinoma development and progression.
  
  
  CONCLUSIONS
  Overall, this study contributes to the understanding of the genetic basis of thyroid carcinoma susceptibility in two different case scenarios such as sMTC and juvenile PTC.
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. berta.luzon.exts@juntadeandalucia.es.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. berta.luzon.exts@juntadeandalucia.es.
authors.forename: Berta
authors.initials: B
authors.lastname: Luzón-Toro
authors.affiliation: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. mb2033@cam.ac.uk.|Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. mb2033@cam.ac.uk.|Present Address: Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, UK. mb2033@cam.ac.uk.
authors.forename: Marta
authors.initials: M
authors.lastname: Bleda
authors.affiliation: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. elena.navarro.sspa@juntadeandalucia.es.|Department of Endocrinology, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. elena.navarro.sspa@juntadeandalucia.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Navarro
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. luzgaral@ebi.ac.uk.|Present Address: European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. luzgaral@ebi.ac.uk.
authors.forename: Luz
authors.initials: L
authors.lastname: García-Alonso
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. mm.ruiz.exts@juntadeandalucia.es.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. mm.ruiz.exts@juntadeandalucia.es.
authors.forename: Macarena
authors.initials: M
authors.lastname: Ruiz-Ferrer
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. im411@cam.ac.uk.|Present Address: HPC Services, University of Cambridge, Cambridge, UK. im411@cam.ac.uk.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Medina
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. martamartin-ibis@us.es.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. martamartin-ibis@us.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Martín-Sánchez
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. cyenyxe@ebi.ac.uk.|Present Address: European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. cyenyxe@ebi.ac.uk.
authors.forename: Cristina Y
authors.initials: CY
authors.lastname: Gonzalez
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. raquelm.fernandez.sspa@juntadeandalucia.es.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. raquelm.fernandez.sspa@juntadeandalucia.es.
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Fernández
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. ana.torroglosa.exts@juntadeandalucia.es.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. ana.torroglosa.exts@juntadeandalucia.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Torroglosa
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. guillermo.antinolo.sspa@juntadeandalucia.es.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. guillermo.antinolo.sspa@juntadeandalucia.es.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Antiñolo
authors.affiliation: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. jdopazo@cipf.es.|Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. jdopazo@cipf.es.|Functional Genomics Node, (INB) at CIPF, Valencia, Spain. jdopazo@cipf.es.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain. salud.borrego.sspa@juntadeandalucia.es.|Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. salud.borrego.sspa@juntadeandalucia.es.
authors.forename: Salud
authors.initials: S
authors.lastname: Borrego
mesh_terms: D000293:Adolescent; D002277:Carcinoma / Q000235:genetics*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics*; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*; D055815:Young Adult