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Identification of four new susceptibility loci for testicular germ cell tumour

Genome-wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify additional single-nucleotide polymorphisms (SNPs) associated with TGCT, we cond...

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Detalles Bibliográficos
Autores principales: Litchfield, Kevin, Holroyd, Amy, Lloyd, Amy, Broderick, Peter, Nsengimana, Jérémie, Eeles, Rosalind, Easton, Douglas F, Dudakia, Darshna, Bishop, D. Timothy, Reid, Alison, Huddart, Robert A., Grotmol, Tom, Wiklund, Fredrik, Shipley, Janet, Houlston, Richard S., Turnbull, Clare
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846317/
https://www.ncbi.nlm.nih.gov/pubmed/26503584
http://dx.doi.org/10.1038/ncomms9690
Descripción
Sumario:Genome-wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify additional single-nucleotide polymorphisms (SNPs) associated with TGCT, we conducted a multistage GWAS with a combined data set of >25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P=1.5 × 10(−9)), 11q14.1 (rs7107174, GAB2, P=9.7 × 10(−11)), 16p13.13 (rs4561483, GSPT1, P=1.6 × 10(−8)) and 16q24.2 (rs55637647, ZFPM1, P=3.4 × 10(−9)). We additionally present detailed functional analysis of these loci, identifying a statistically significant relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biological basis of disease development.