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Runs of homozygosity and inbreeding in thyroid cancer

Thomsen, Hauke LU ; Chen, Bowang LU ; Figlioli, Gisella; Elisei, Rossella; Romei, Cristina; Cipollini, Monica; Cristaudo, Alfonso; Bambi, Franco; Hoffmann, Per and Herms, Stefan, et al. (2016) In BMC Cancer 16(1).
Abstract

Background: Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) influencing the risk of thyroid cancer (TC). Most cancer predisposition genes identified through GWASs function in a co-dominant manner, and studies have not found evidence for recessively functioning disease loci in TC. Our study examines whether homozygosity is associated with an increased risk of TC and searches for novel recessively acting disease loci. Methods: Data from a previously conducted GWAS were used for the estimation of the proportion of phenotypic variance explained by all common SNPs, the detection of runs of homozygosity (ROH) and the determination of inbreeding to unravel their influence on TC. Results:... (More)

Background: Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) influencing the risk of thyroid cancer (TC). Most cancer predisposition genes identified through GWASs function in a co-dominant manner, and studies have not found evidence for recessively functioning disease loci in TC. Our study examines whether homozygosity is associated with an increased risk of TC and searches for novel recessively acting disease loci. Methods: Data from a previously conducted GWAS were used for the estimation of the proportion of phenotypic variance explained by all common SNPs, the detection of runs of homozygosity (ROH) and the determination of inbreeding to unravel their influence on TC. Results: Inbreeding coefficients were significantly higher among cases than controls. Association on a SNP-by-SNP basis was controlled by using the false discovery rate at a level of q* < 0.05, with 34 SNPs representing true differences in homozygosity between cases and controls. The average size, the number and total length of ROHs per person were significantly higher in cases than in controls. A total of 16 recurrent ROHs of rather short length were identified although their association with TC risk was not significant at a genome-wide level. Several recurrent ROHs harbor genes associated with risk of TC. All of the ROHs showed significant evidence for natural selection (iHS, Fst, Fay and Wu's H). Conclusions: Our results support the existence of recessive alleles in TC susceptibility. Although regions of homozygosity were rather small, it might be possible that variants within these ROHs affect TC risk and may function in a recessive manner.

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GWAS, Inbreeding, Runs of homozygosity, Thyroid cancer
in
BMC Cancer
volume
16
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85007500951
  • wos:000372089300004
ISSN
1471-2407
DOI
10.1186/s12885-016-2264-7
language
English
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yes
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52a25479-cf58-4122-903e-9818bf6cd178
date added to LUP
2017-01-19 12:20:06
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2017-09-18 11:32:36
@article{52a25479-cf58-4122-903e-9818bf6cd178,
  abstract     = {<p>Background: Genome-wide association studies (GWASs) have identified several single-nucleotide polymorphisms (SNPs) influencing the risk of thyroid cancer (TC). Most cancer predisposition genes identified through GWASs function in a co-dominant manner, and studies have not found evidence for recessively functioning disease loci in TC. Our study examines whether homozygosity is associated with an increased risk of TC and searches for novel recessively acting disease loci. Methods: Data from a previously conducted GWAS were used for the estimation of the proportion of phenotypic variance explained by all common SNPs, the detection of runs of homozygosity (ROH) and the determination of inbreeding to unravel their influence on TC. Results: Inbreeding coefficients were significantly higher among cases than controls. Association on a SNP-by-SNP basis was controlled by using the false discovery rate at a level of q* &lt; 0.05, with 34 SNPs representing true differences in homozygosity between cases and controls. The average size, the number and total length of ROHs per person were significantly higher in cases than in controls. A total of 16 recurrent ROHs of rather short length were identified although their association with TC risk was not significant at a genome-wide level. Several recurrent ROHs harbor genes associated with risk of TC. All of the ROHs showed significant evidence for natural selection (iHS, Fst, Fay and Wu's H). Conclusions: Our results support the existence of recessive alleles in TC susceptibility. Although regions of homozygosity were rather small, it might be possible that variants within these ROHs affect TC risk and may function in a recessive manner.</p>},
  articleno    = {227},
  author       = {Thomsen, Hauke and Chen, Bowang and Figlioli, Gisella and Elisei, Rossella and Romei, Cristina and Cipollini, Monica and Cristaudo, Alfonso and Bambi, Franco and Hoffmann, Per and Herms, Stefan and Landi, Stefano and Hemminki, Kari and Gemignani, Federica and Försti, Asta},
  issn         = {1471-2407},
  keyword      = {GWAS,Inbreeding,Runs of homozygosity,Thyroid cancer},
  language     = {eng},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {Runs of homozygosity and inbreeding in thyroid cancer},
  url          = {http://dx.doi.org/10.1186/s12885-016-2264-7},
  volume       = {16},
  year         = {2016},
}