Abstract
BackgroundGastro-oesophageal reflux disease (GORD) is associated with multiple risk factors but determining causality is difficult. We used a genetic approach [Mendelian randomization (MR)] to identify potential causal modifiable risk factors for GORD.MethodsWe used data from 451 097 European participants in the UK Biobank and defined GORD using hospital-defined ICD10 and OPCS4 codes and self-report data (N = 41 024 GORD cases). We tested observational and MR-based associations between GORD and four adiposity measures [body mass index (BMI), waist–hip ratio (WHR), a metabolically favourable higher body-fat percentage and waist circumference], smoking status, smoking frequency and caffeine consumption.ResultsObservationally, all adiposity measures were associated with higher odds of GORD. Ever and current smoking were associated with higher odds of GORD. Coffee consumption was associated with lower odds of GORD but, among coffee drinkers, more caffeinated-coffee consumption was associated with higher odds of GORD. Using MR, we provide strong evidence that higher WHR and higher WHR adjusted for BMI lead to GORD. There was weak evidence that higher BMI, body-fat percentage, coffee drinking or smoking caused GORD, but only the observational effects for BMI and body-fat percentage could be excluded. This MR estimated effect for WHR equates to a 1.23-fold higher odds of GORD per 5-cm increase in waist circumference.ConclusionsThese results provide strong evidence that a higher waist–hip ratio leads to GORD. Our study suggests that central fat distribution is crucial in causing GORD rather than overall weight.
Highlights
Gastroesophageal reflux disease (GORD) has been defined as ‘symptoms or complications resulting from the reflux of gastric contents into the oesophagus or beyond, into the oral cavity or lung’.1 Gastro-oesophageal reflux disease (GORD) is common, with typical symptoms of heartburn and acid regurgitation reported weekly by 13.3% of the general population.[2]Numerous modifiable risk factors have been demonstrated to associate with GORD, but the majority of these have only been reported in observational studies, which are prone to confounding and reverse causality
Several observational studies report an attenuation in the body mass index (BMI) association when BMI and waist–hip ratio (WHR) are included in multivariable models, suggesting that body-fat distribution may be an important factor in GORD.[6]
International Classification of Diseases 10th Revision (ICD10) and OPCS Classification of Interventions and Procedures version 4 (OPCS4) operation codes were obtained from the Hospital Episode Statistics (HES; https://digital.nhs.uk/ data-and-information/data-tools-and-services/data-services/ hospital-episode-statistics)
Summary
Gastroesophageal reflux disease (GORD) has been defined as ‘symptoms or complications resulting from the reflux of gastric contents into the oesophagus or beyond, into the oral cavity (including larynx) or lung’.1 GORD is common, with typical symptoms of heartburn and acid regurgitation reported weekly by 13.3% of the general population.[2]Numerous modifiable risk factors have been demonstrated to associate with GORD, but the majority of these have only been reported in observational studies, which are prone to confounding and reverse causality. A large meta-analysis of 22 studies reports a 1.73fold (1.46–2.06) increased risk of GORD in obese individuals (defined by BMI > 30 kg/m2)[2] and a recent large genome-wide association study (GWAS) of GORD reports a genetic correlation between GORD and BMI.[3] The literature provides evidence that other measures of adiposity correlate with GORD phenotypes including waist circumference with reflux symptoms[4] and waist–hip ratio (WHR) with both oesophageal inflammation (erosive reflux disease) and Barrett’s Oesophagus.[5] Several observational studies report an attenuation in the BMI association when BMI and WHR are included in multivariable models, suggesting that body-fat distribution may be an important factor in GORD.[6]. There was weak evidence that higher BMI, body-fat percentage, coffee drinking or smoking caused GORD, but only the observational effects for BMI and body-fat percentage could be excluded This MR estimated effect for WHR equates to a 1.23-fold higher odds of GORD per 5-cm increase in waist circumference. Our study suggests that central fat distribution is crucial in causing GORD rather than overall weight
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
