title: Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus.
abstract: Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3-11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA.
authors.affiliation: Statistical Genetics Laboratory, puya.gharahkhani@qimrberghofer.edu.au.
authors.forename: Puya
authors.initials: P
authors.lastname: Gharahkhani
authors.affiliation: 23andMe, Mountain View, CA 94035, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Tung
authors.affiliation: 23andMe, Mountain View, CA 94035, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hinds
authors.affiliation: Statistical Genetics Laboratory, Department of Complex Trait Genetics, VU University, Center for Neurogenomics and Cognitive Research, Amsterdam, The Netherlands and.
authors.forename: Aniket
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
authors.affiliation: Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
authors.affiliation: Statistical Genetics Laboratory.
authors.forename: Stuart
authors.initials: S
authors.lastname: MacGregor
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D001471:Barrett Esophagus / Q000235:genetics*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D005764:Gastroesophageal Reflux / Q000235:genetics*; D056726:Genetic Association Studies; D000068617:Genetic Background; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics