{"id":{"repo_id":"plymouth","oai_identifier":"oai:pearl.plymouth.ac.uk:pms-theses-1027"},"canonical_url":"https://search.dev.ndltd.org/etd/plymouth/oai:pearl.plymouth.ac.uk:pms-theses-1027","repository":{"repo_id":"plymouth","name":"University of Plymouth","base_url":"https://pearl.plymouth.ac.uk/do/oai"},"display":{"title":"Identification of Two Novel Genome-Wide Significant Single Nucleotide Polymorphisms, associated with Barrett’s Oesophagus, determined by further Replication of a Genome-Wide Association Study","abstract":"Barrett's oesophagus (BE) is a common premalignant condition to oesophageal adenocarcinoma (EAC). A previous genome-wide association study (GWAS) identified BE susceptibility Single Nucleotide Polymorphisms (SNPs) on chromosome 6p21, within the HLA region, and16q23, where the closest protein-coding gene was FOXF1. The replication study outlined in this thesis aimed to identify possible additional variants that did not reach genome-wide significance in the GWAS, in up to 10,158 BE patients and 21,062 controls. Meta-analysis of the data identified two further BE susceptibility SNPs: rs3072 (2p24.1; 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 two closest protein-coding genes, and most likely functional targets, are the bone morphogenetic protein pathway ligand GDF7 (rs3072) and TBX5 (rs2701108). A second GWAS of combined BE and EAC cases was recently published, analysing a total of 922,031 SNPs, where 87 of 94 associated SNPs with P<1×10−4 were selected for further replication, identified four SNPs (three loci) with BE/EAC risk in CRTC1 and BARX1 and within 100kb of FOXP1. Our data supported three of the BE/EAC associated SNPs and meta-analysis of all 87 SNPs detected a further susceptibility locus, rs3784262, near ALDH1A2 (OR=0.90, 95%CI 0.87-0.93, P=3.72×10−9). Overall, two novel BE susceptibility loci have been identified and data has been provided to support three previously identified BE/EAC SNPs and one additional BE/EAC locus. To date, genes implicated in BE susceptibility appear to encode transcription factors involved in thoracic, diaphragmatic and oesophageal development or inflammatory response proteins.","abstract_html":"Barrett's oesophagus (BE) is a common premalignant condition to oesophageal adenocarcinoma (EAC). A previous genome-wide association study (GWAS) identified BE susceptibility Single Nucleotide Polymorphisms (SNPs) on chromosome 6p21, within the HLA region, and16q23, where the closest protein-coding gene was FOXF1. The replication study outlined in this thesis aimed to identify possible additional variants that did not reach genome-wide significance in the GWAS, in up to 10,158 BE patients and 21,062 controls. Meta-analysis of the data identified two further BE susceptibility SNPs: rs3072 (2p24.1; 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 two closest protein-coding genes, and most likely functional targets, are the bone morphogenetic protein pathway ligand GDF7 (rs3072) and TBX5 (rs2701108). A second GWAS of combined BE and EAC cases was recently published, analysing a total of 922,031 SNPs, where 87 of 94 associated SNPs with P<1×10−4 were selected for further replication, identified four SNPs (three loci) with BE/EAC risk in CRTC1 and BARX1 and within 100kb of FOXP1. Our data supported three of the BE/EAC associated SNPs and meta-analysis of all 87 SNPs detected a further susceptibility locus, rs3784262, near ALDH1A2 (OR=0.90, 95%CI 0.87-0.93, P=3.72×10−9). Overall, two novel BE susceptibility loci have been identified and data has been provided to support three previously identified BE/EAC SNPs and one additional BE/EAC locus. To date, genes implicated in BE susceptibility appear to encode transcription factors involved in thoracic, diaphragmatic and oesophageal development or inflammatory response proteins.","abstract_has_math":false,"creators":["Chegwidden, Laura"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Elaine Green, Simon Jackson, Janusz Jankowski"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-01-01T08:00:00Z","date_published":"2015-01-01T08:00:00Z","updated_at":"2026-07-24T03:48:35Z","subjects":["Barrett's Oesophagus","Cancer","Genetics","Genome-Wide Association Study","Single Nucleotide Polymorphisms"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://pearl.plymouth.ac.uk/pms-theses/28","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Elaine Green, Simon Jackson, Janusz Jankowski"]},{"key":"dc:creator","label":"Author","values":["Chegwidden, Laura"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2015-01-01T08:00:00Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Barrett's Oesophagus","Cancer","Genetics","Genome-Wide Association Study","Single Nucleotide Polymorphisms"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://pearl.plymouth.ac.uk/pms-theses/28"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Barrett's oesophagus (BE) is a common premalignant condition to oesophageal adenocarcinoma (EAC). A previous genome-wide association study (GWAS) identified BE susceptibility Single Nucleotide Polymorphisms (SNPs) on chromosome 6p21, within the HLA region, and16q23, where the closest protein-coding gene was FOXF1. The replication study outlined in this thesis aimed to identify possible additional variants that did not reach genome-wide significance in the GWAS, in up to 10,158 BE patients and 21,062 controls. Meta-analysis of the data identified two further BE susceptibility SNPs: rs3072 (2p24.1; 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 two closest protein-coding genes, and most likely functional targets, are the bone morphogenetic protein pathway ligand GDF7 (rs3072) and TBX5 (rs2701108). A second GWAS of combined BE and EAC cases was recently published, analysing a total of 922,031 SNPs, where 87 of 94 associated SNPs with P<1×10−4 were selected for further replication, identified four SNPs (three loci) with BE/EAC risk in CRTC1 and BARX1 and within 100kb of FOXP1. Our data supported three of the BE/EAC associated SNPs and meta-analysis of all 87 SNPs detected a further susceptibility locus, rs3784262, near ALDH1A2 (OR=0.90, 95%CI 0.87-0.93, P=3.72×10−9). Overall, two novel BE susceptibility loci have been identified and data has been provided to support three previously identified BE/EAC SNPs and one additional BE/EAC locus. To date, genes implicated in BE susceptibility appear to encode transcription factors involved in thoracic, diaphragmatic and oesophageal development or inflammatory response proteins."]},{"key":"dc:title","label":"Title","values":["Identification of Two Novel Genome-Wide Significant Single Nucleotide Polymorphisms, associated with Barrett’s Oesophagus, determined by further Replication of a Genome-Wide Association Study"]}]}],"canonical_facts":{"dc:contributor":["Elaine Green, Simon Jackson, Janusz Jankowski"],"dc:creator":["Chegwidden, Laura"],"dc:date.issued":["2015-01-01T08:00:00Z"],"dc:description.abstract":["Barrett's oesophagus (BE) is a common premalignant condition to oesophageal adenocarcinoma (EAC). A previous genome-wide association study (GWAS) identified BE susceptibility Single Nucleotide Polymorphisms (SNPs) on chromosome 6p21, within the HLA region, and16q23, where the closest protein-coding gene was FOXF1. The replication study outlined in this thesis aimed to identify possible additional variants that did not reach genome-wide significance in the GWAS, in up to 10,158 BE patients and 21,062 controls. Meta-analysis of the data identified two further BE susceptibility SNPs: rs3072 (2p24.1; 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 two closest protein-coding genes, and most likely functional targets, are the bone morphogenetic protein pathway ligand GDF7 (rs3072) and TBX5 (rs2701108). A second GWAS of combined BE and EAC cases was recently published, analysing a total of 922,031 SNPs, where 87 of 94 associated SNPs with P<1×10−4 were selected for further replication, identified four SNPs (three loci) with BE/EAC risk in CRTC1 and BARX1 and within 100kb of FOXP1. Our data supported three of the BE/EAC associated SNPs and meta-analysis of all 87 SNPs detected a further susceptibility locus, rs3784262, near ALDH1A2 (OR=0.90, 95%CI 0.87-0.93, P=3.72×10−9). Overall, two novel BE susceptibility loci have been identified and data has been provided to support three previously identified BE/EAC SNPs and one additional BE/EAC locus. To date, genes implicated in BE susceptibility appear to encode transcription factors involved in thoracic, diaphragmatic and oesophageal development or inflammatory response proteins."],"dc:identifier":["https://pearl.plymouth.ac.uk/pms-theses/28"],"dc:language":["eng"],"dc:subject":["Barrett's Oesophagus","Cancer","Genetics","Genome-Wide Association Study","Single Nucleotide Polymorphisms"],"dc:title":["Identification of Two Novel Genome-Wide Significant Single Nucleotide Polymorphisms, associated with Barrett’s Oesophagus, determined by further Replication of a Genome-Wide Association Study"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T03:48:35Z"}