Runs of homozygosity and inbreeding in thyroid cancer.

Authors:
Hauke Thomsen, Dr.
Hauke Thomsen, Dr.
GeneWerk GmbH
Senior Bioinformatician
Bioinformatics, Biostatistics, Genetics
Heidelberg, Baden-Württemberg/Germany | Germany
Bowang Chen
Bowang Chen
University of Heidelberg
Germany
Gisella Figlioli
Gisella Figlioli
University of Pisa
Italy
Rossella Elisei
Rossella Elisei
University of Pisa
Pisa | Italy
Cristina Romei
Cristina Romei
University of Pisa
Italy
Monica Cipollini
Monica Cipollini
University of Pisa
Italy
Alfonso Cristaudo
Alfonso Cristaudo
University of Pisa
Italy
Franco Bambi
Franco Bambi
University of Florence
Italy

BMC Cancer 2016 Mar 16;16:227. Epub 2016 Mar 16.

Molecular Genetic Epidemiology, C050, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany.

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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Source
http://dx.doi.org/10.1186/s12885-016-2264-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794977PMC

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March 2016
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