Buscar

 Detalle_Publicacion

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Abstract: Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Nat Commun. 2018 Jun 11;9(1):2256

Editorial: Nature Publishing Group

 Año de publicación: 2018

Nº de páginas: 19

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41467-018-04109-8

ISSN: 2041-1723

Url de la publicación: https://dx.doi.org/10.1038/s41467-018-04109-8

Autores/as

DADAEV, TOKHIR

SAUNDERS, EDWARD J.

NEWCOMBE, PAUL J.

ANOKIAN, EZEQUIEL

LEONGAMORNLERT, DANIEL A.

BROOK, MARK N.

CIEZA-BORRELLA, CLARA

MIJUSKOVIC, MARTINA

WAKERELL, SARAH

OLAMA, ALI AMIN AL

SCHUMACHER, FREDRICK R.

BERNDT, SONJA I.

BENLLOCH, SARA

AHMED, MAHBUBL

GOH, CHEE

SHENG, XIN