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BMC Med Genomics. 2015 Dec 21;8:83. doi: 10.1186/s12920-015-0160-7.

Identification of epistatic interactions through genome-wide association studies in sporadic medullary and juvenile papillary thyroid carcinomas.

Author information

1
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.
2
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. berta.luzon.exts@juntadeandalucia.es.
3
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. mb2033@cam.ac.uk.
4
Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. mb2033@cam.ac.uk.
5
Present Address: Department of Medicine, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, UK. mb2033@cam.ac.uk.
6
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. elena.navarro.sspa@juntadeandalucia.es.
7
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.
8
Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. luzgaral@ebi.ac.uk.
9
Present Address: European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. luzgaral@ebi.ac.uk.
10
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.
11
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. mm.ruiz.exts@juntadeandalucia.es.
12
Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. im411@cam.ac.uk.
13
Present Address: HPC Services, University of Cambridge, Cambridge, UK. im411@cam.ac.uk.
14
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.
15
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. martamartin-ibis@us.es.
16
Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. cyenyxe@ebi.ac.uk.
17
Present Address: European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. cyenyxe@ebi.ac.uk.
18
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.
19
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. raquelm.fernandez.sspa@juntadeandalucia.es.
20
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.
21
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. ana.torroglosa.exts@juntadeandalucia.es.
22
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.
23
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. guillermo.antinolo.sspa@juntadeandalucia.es.
24
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. jdopazo@cipf.es.
25
Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), C/Eduardo Primo Yúfera, 3, 46012, Valencia, Spain. jdopazo@cipf.es.
26
Functional Genomics Node, (INB) at CIPF, Valencia, Spain. jdopazo@cipf.es.
27
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.
28
Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. salud.borrego.sspa@juntadeandalucia.es.

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.

PMID:
26690675
PMCID:
PMC4685628
DOI:
10.1186/s12920-015-0160-7
[Indexed for MEDLINE]
Free PMC Article

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