Fine-Mapping the HOXB Region Detects Common Variants Tagging a Rare Coding Allele: Evidence for Synthetic Association in Prostate Cancer

Edward J Saunders; Tokhir Dadaev; Daniel A Leongamornlert; Sarah Jugurnauth-Little; Malgorzata Tymrakiewicz; Fredrik Wiklund; Ali Amin Al Olama; Sara Benlloch; David E Neal; Freddie C Hamdy; Jenny L Donovan; Graham G Giles; Gianluca Severi; Henrik Gronberg; Markus Aly; Christopher A Haiman; Fredrick Schumacher; Brian E Henderson; Sara Lindstrom; Peter Kraft; David J Hunter; Susan Gapstur; Stephen Chanock; Sonja I Berndt; Demetrius Albanes; Gerald Andriole; Johanna Schleutker; Maren Weischer; Borge G Nordestgaard; Federico Canzian; Daniele Campa; Elio Riboli; Tim J Key; Ruth C Travis; Sue A Ingles; Esther M John; Richard B Hayes; Paul Pharoah; Kay-Tee Khaw; Janet L Stanford; Elaine A Ostrander; Lisa B Signorello; Stephen N Thibodeau; Daniel Schaid; Christiane Maier; Adam S Kibel; Cezary Cybulski; Lisa Cannon-Albright; Hermann Brenner; Jong Y Park; Radka Kaneva; Jyotsna Batra; Judith A Clements; Manuel R Teixeira; Jianfeng Xu; Christos Mikropoulos; Chee Goh; Koveela Govindasami; Michelle Guy; Rosemary A Wilkinson; Emma J Sawyer; Angela Morgan; Douglas F Easton; Ken Muir; Rosalind A Eeles; Zsofia Kote-Jarai

Journal article

Fine-Mapping the HOXB Region Detects Common Variants Tagging a Rare Coding Allele: Evidence for Synthetic Association in Prostate Cancer

Edward J Saunders, Tokhir Dadaev, Daniel A Leongamornlert, Sarah Jugurnauth-Little, Malgorzata Tymrakiewicz, Fredrik Wiklund, Ali Amin Al Olama, Sara Benlloch, David E Neal, Freddie C Hamdy, Jenny L Donovan, Graham G Giles, Gianluca Severi, Henrik Gronberg, Markus Aly, Christopher A Haiman, Fredrick Schumacher, Brian E Henderson, Sara Lindstrom, Peter Kraft Show all

PLOS GENETICS | PUBLIC LIBRARY SCIENCE | Published : 2014

DOI: 10.1371/journal.pgen.1004129

Abstract

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regre..

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University of Melbourne Researchers

Graham Giles Author Melbourne School of Population and Global Health

Gianluca Severi Author Melbourne School of Population and Global Health

Grants

Awarded by Cancer Research UK

Awarded by MRC

Awarded by Medical Research Council

Awarded by National Institute for Health Research

Awarded by The Francis Crick Institute

Awarded by NATIONAL CANCER INSTITUTE

Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE

Funding Acknowledgements

This work was supported by EU-FP7 COGS grant. Cancer Research UK grants C5047/A15007 supported the team at ICR, C8197/A10123 and C8197/A10865 supported the genotyping team in Cambridge. For more funding details for individual groups within the PRACTICAL consortium please see Supplementary file S2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.