New basal cell carcinoma susceptibility loci

نویسندگان

  • Simon N. Stacey
  • Hannes Helgason
  • Sigurjon A. Gudjonsson
  • Gudmar Thorleifsson
  • Florian Zink
  • Asgeir Sigurdsson
  • Birte Kehr
  • Julius Gudmundsson
  • Patrick Sulem
  • Bardur Sigurgeirsson
  • Kristrun R. Benediktsdottir
  • Kristin Thorisdottir
  • Rafn Ragnarsson
  • Victoria Fuentelsaz
  • Cristina Corredera
  • Yolanda Gilaberte
  • Matilde Grasa
  • Dolores Planelles
  • Onofre Sanmartin
  • Peter Rudnai
  • Eugene Gurzau
  • Kvetoslava Koppova
  • Bjørn A. Nexø
  • Anne Tjønneland
  • Kim Overvad
  • Jon G. Jonasson
  • Laufey Tryggvadottir
  • Hrefna Johannsdottir
  • Anna M. Kristinsdottir
  • Hreinn Stefansson
  • Gisli Masson
  • Olafur T. Magnusson
  • Bjarni V. Halldorsson
  • Augustine Kong
  • Thorunn Rafnar
  • Unnur Thorsteinsdottir
  • Ulla Vogel
  • Rajiv Kumar
  • Eduardo Nagore
  • José I. Mayordomo
  • Daniel F. Gudbjartsson
  • Jon H. Olafsson
  • Kari Stefansson
چکیده

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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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015