Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Zhan Su, Laura J Gay, Amy Strange, Claire Palles, Gavin Band, David C Whiteman, Francesco Lescai, Cordelia Langford, Manoj Nanji, Sarah Edkins, Anouk van der Winkel, David Levine (+132 others)
2012 Nature Genetics  
Barrett's Esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia. Barrett's Esophagus strongly predisposes to esophageal adenocarcinoma (EAC), a tumour with a very poor prognosis. We have undertaken the first genome-wide association study on Barrett's Esophagus, comprising 1,852 UK cases and 5,172 UK controls in discovery and 5,986 cases and 12,825 controls in the replication. Two regions were associated with disease risk:
more » ... with disease risk: chromosome 6p21, rs9257809 (P combined =4.09×10 −9 , OR(95%CI) =1.21(1.13-1.28)) and chromosome 16q24, rs9936833 (P combined =2.74×10 −10 , OR(95%CI) =1.14(1.10-1.19)). The top SNP on chromosome 6p21 is within the major histocompatibility complex, and the closest protein-coding gene to rs9936833 on chromosome 16q24 is FOXF1, which is implicated in esophageal development and structure. We found evidence that the genetic component of Barrett's Esophagus is mediated by many common variants of small effect and that SNP alleles predisposing to obesity also increase risk for Barrett's Esophagus. .) monitored the appropriate use of samples and data from these studies. A. van der Winkel, N.T., M.P.Peppelenbosch, L.J.
doi:10.1038/ng.2408 pmid:22961001 pmcid:PMC3459818 fatcat:mud5ejz6yzgwpcmacot36g24dy