Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.
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Palles Claire, Chegwidden Laura, Li Xinzhong, Findlay John M, Farnham Garry, Castro Giner Francesc, Peppelenbosch Maikel P, Kovac Michal, Adams Claire L, Prenen Hans, Briggs Sarah, Harrison Rebecca, Sanders Scott, MacDonald David, Haigh Chris, Tucker Art, Love Sharon, Nanji Manoj, deCaestecker John, Ferry David, Rathbone Barrie, Hapeshi Julie, Barr Hugh, Moayyedi Paul, Watson Peter, Zietek Barbara, Maroo Neera, Gay Laura, Underwood Tim, Boulter Lisa, McMurtry Hugh, Monk David, Patel Praful, Ragunath Krish, Al Dulaimi David, Murray Iain, Koss Konrad, Veitch Andrew, Trudgill Nigel, Nwokolo Chuka, Rembacken Bjorn, Atherfold Paul, Green Elaine, Ang Yeng, Kuipers Ernst J, Chow Wu, Paterson Stuart, Kadri Sudarshan, Beales Ian, Grimley Charles, Mullins Paul, Beckett Conrad, Farrant Mark, Dixon Andrew, Kelly Sean, Johnson Matthew, Wajed Shahjehan, Dhar Anjan, Sawyer Elinor, Roylance Rebecca, Onstad Lynn, Gammon Marilie D, Corley Douglas A, Shaheen Nicholas J, Bird Nigel C, Hardie Laura J, Reid Brian J, Ye Weimin, Liu Geoffrey, Romero Yvonne, Bernstein Leslie, Wu Anna H, Casson Alan G, Fitzgerald Rebecca, Whiteman David C, Risch Harvey A, Levine David M, Vaughan Tom L, Verhaar Auke P, van den Brande Jan, Toxopeus Eelke L, Spaander Manon C, Wijnhoven Bas P L, van der Laan Luc J W, Krishnadath Kausilia, Wijmenga Cisca, Trynka Gosia, McManus Ross, Reynolds John V, O'Sullivan Jacintha, MacMathuna Padraic, McGarrigle Sarah A, Kelleher Dermot, Vermeire Severine, Cleynen Isabelle, Bisschops Raf, Tomlinson Ian, Jankowski Janusz
Аннотация
METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.
RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).
CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.