| Literature DB >> 25855136 |
Simon N Stacey1, Hannes Helgason1, Sigurjon A Gudjonsson1, Gudmar Thorleifsson1, Florian Zink1, Asgeir Sigurdsson1, Birte Kehr1, Julius Gudmundsson1, Patrick Sulem1, Bardur Sigurgeirsson2, Kristrun R Benediktsdottir2, Kristin Thorisdottir2, Rafn Ragnarsson2, Victoria Fuentelsaz3, Cristina Corredera4, Yolanda Gilaberte5, Matilde Grasa6, Dolores Planelles7, Onofre Sanmartin8, Peter Rudnai9, Eugene Gurzau10, Kvetoslava Koppova11, Bjørn A Nexø12, Anne Tjønneland13, Kim Overvad14, Jon G Jonasson15, Laufey Tryggvadottir16, Hrefna Johannsdottir1, Anna M Kristinsdottir1, Hreinn Stefansson1, Gisli Masson1, Olafur T Magnusson1, Bjarni V Halldorsson17, Augustine Kong1, Thorunn Rafnar1, Unnur Thorsteinsdottir18, Ulla Vogel19, Rajiv Kumar20, Eduardo Nagore8, José I Mayordomo21, Daniel F Gudbjartsson1, Jon H Olafsson2, Kari Stefansson18.
Abstract
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.Entities:
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Year: 2015 PMID： 25855136 PMCID： PMC4403348 DOI： 10.1038/ncomms7825
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919