Quantifying the heritability of testicular germ cell tumour using both population-based and genomic approaches.

Authors:
Kevin Litchfield
Kevin Litchfield
Institute of Cancer Research
Hauke Thomsen, Dr.
Hauke Thomsen, Dr.
GeneWerk GmbH
Senior Bioinformatician
Bioinformatics, Biostatistics, Genetics
Heidelberg, Baden-Württemberg/Germany | Germany
Jonathan S Mitchell
Jonathan S Mitchell
The University of Chicago
United States
Jan Sundquist
Jan Sundquist
Stanford University School of Medicine
Sweden
Richard S Houlston
Richard S Houlston
The Institute of Cancer Research
United Kingdom
Kari Hemminki
Kari Hemminki
German Cancer Research Center (DKFZ)
Heidelberg | Germany
Clare Turnbull
Clare Turnbull
Institute of Cancer Research
United Kingdom

Sci Rep 2015 Sep 9;5:13889. Epub 2015 Sep 9.

Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW3 6JB, UK.

A sizable fraction of testicular germ cell tumour (TGCT) risk is expected to be explained by heritable factors. Recent genome-wide association studies (GWAS) have successfully identified a number of common SNPs associated with TGCT. It is however, unclear how much common variation there is left to be accounted for by other, yet to be identified, common SNPs and what contribution common genetic variation makes to the heritable risk of TGCT. We approached this question using two complimentary analytical techniques. We undertook a population-based analysis of the Swedish family-cancer database, through which we estimated that the heritability of TGCT at 48.9% (CI:47.2%-52.3%). We also applied Genome-Wide Complex Trait Analysis to 922 cases and 4,842 controls to estimate the heritability of TGCT. The heritability explained by known common risk SNPs identified by GWAS was 9.1%, whereas the heritability explained by all common SNPs was 37.4% (CI:27.6%-47.2%). These complementary findings indicate that the known TGCT SNPs only explain a small proportion of the heritability and many additional common SNPs remain to be identified. The data also suggests that a fraction of the heritability of TGCT is likely to be explained by other classes of genetic variation, such as rare disease-causing alleles.

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Source
http://dx.doi.org/10.1038/srep13889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563562PMC

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September 2015
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