Recurrent Coding Sequence Variation Explains Only A Small Fraction of the Genetic Architecture of Colorectal Cancer

@article{Timofeeva2015RecurrentCS,
  title={Recurrent Coding Sequence Variation Explains Only A Small Fraction of the Genetic Architecture of Colorectal Cancer},
  author={Maria N Timofeeva and Ben Kinnersley and Susan M. Farrington and Nicola Whiffin and Claire Palles and Victoria Svinti and Amy L. Lloyd and Maggie Gorman and Li Yin Ooi and Fay J. Hosking and Ella Barclay and Lina Zgaga and Sara E. Dobbins and Lynn Martin and Evropi Theodoratou and Peter Broderick and Albert Tenesa and Claire L Smillie and Graeme Grimes and Caroline Hayward and Archie I Campbell and David J. Porteous and Ian J. Deary and Sarah E. Harris and Emma L. Northwood and Jennifer H. Barrett and Gillian Smith and Roland Wolf and David Forman and Hans Morreau and Dina Ruano and Carli M.J. Tops and Juul Th. Wijnen and Melanie Schrumpf and Arnoud Boot and Hans F A Vasen and Frederik J. Hes and Tom van Wezel and Andr{\'e} Franke and W. Lieb and Clemens Schafmayer and Jochen Hampe and Stephan Buch and P. Propping and Kari Hemminki and Asta F{\"o}rsti and Helga Westers and Robert M.W. Hofstra and Manuela Pinheiro and Carla Pinto and Manuel R. Teixeira and Clara Ruiz-Ponte and Ceres Fern{\'a}ndez-Rozadilla and {\'A}ngel Carracedo and Antoni Castells and Sergi Castellv{\'i}-Bel and Harry Campbell and D. Timothy Bishop and Ian P. M. Tomlinson and Malcolm G. Dunlop and Richard S. Houlston},
  journal={Scientific Reports},
  year={2015},
  volume={5}
}
Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10−7), and novel damaging… 
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