New basal cell carcinoma susceptibility loci

In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358...

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Detalles Bibliográficos
Autores principales: Stacey, Simon N., Helgason, Hannes, Gudjonsson, Sigurjon A., Thorleifsson, Gudmar, Zink, Florian, Sigurdsson, Asgeir, Kehr, Birte, Gudmundsson, Julius, Sulem, Patrick, Sigurgeirsson, Bardur, Benediktsdottir, Kristrun R., Thorisdottir, Kristin, Ragnarsson, Rafn, Fuentelsaz, Victoria, Corredera, Cristina, Gilaberte, Yolanda, Grasa, Matilde, Planelles, Dolores, Sanmartin, Onofre, Rudnai, Peter, Gurzau, Eugene, Koppova, Kvetoslava, Nexø, Bjørn A., Tjønneland, Anne, Overvad, Kim, Jonasson, Jon G., Tryggvadottir, Laufey, Johannsdottir, Hrefna, Kristinsdottir, Anna M., Stefansson, Hreinn, Masson, Gisli, Magnusson, Olafur T., Halldorsson, Bjarni V., Kong, Augustine, Rafnar, Thorunn, Thorsteinsdottir, Unnur, Vogel, Ulla, Kumar, Rajiv, Nagore, Eduardo, Mayordomo, José I., Gudbjartsson, Daniel F., Olafsson, Jon H., Stefansson, Kari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403348/
https://www.ncbi.nlm.nih.gov/pubmed/25855136
http://dx.doi.org/10.1038/ncomms7825
Descripción
Sumario:In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(−12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(−9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(−12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(−16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.

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