Quantifying the heritability of testicular germ cell tumour using both population-based and genomic approaches.
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.
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW3 6JB, UK.
Kevin
K
Litchfield
German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology, Heidelberg, Germany.
Hauke
H
Thomsen
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW3 6JB, UK.
Jonathan S
JS
Mitchell
Center for Primary Health Care Research, Lund University, Malmö, Sweden.|Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA.
Jan
J
Sundquist
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW3 6JB, UK.
Richard S
RS
Houlston
German Cancer Research Center (DKFZ), Division of Molecular Genetic Epidemiology, Heidelberg, Germany.|Center for Primary Health Care Research, Lund University, Malmö, Sweden.
Kari
K
Hemminki
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW3 6JB, UK.|William Harvey research Centre, Queen Mary University London, London.
Clare
C
Turnbull
D002874:Chromosome Mapping; D016208:Databases, Factual; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance / Q000379:methods; D013548:Sweden / Q000453:epidemiology; D013736:Testicular Neoplasms / Q000453:epidemiology* / Q000235:genetics*