Genetic evidence that higher central adiposity causes gastro-oesophageal reflux disease: a Mendelian randomization study

被引:22
作者
Green, Harry D. [1 ,2 ]
Beaumont, Robin N. [1 ]
Wood, Andrew R. [1 ]
Hamilton, Benjamin [2 ]
Jones, Samuel E. [1 ]
Goodhand, James R. [2 ]
Kennedy, Nicholas A. [2 ]
Ahmad, Tariq [2 ]
Yaghootkar, Hanieh [1 ]
Weedon, Michael N. [1 ]
Frayling, Timothy M. [1 ]
Tyrrell, Jessica [1 ]
机构
[1] Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England
[2] Royal Devon & Exeter NHS Fdn Trust, IBD Pharmacogenet, Exeter, Devon, England
基金
欧洲研究理事会; 英国惠康基金; 英国医学研究理事会;
关键词
GORD; UK Biobank; Mendelian randomization; adiposity; epidemiology; gastroenterology; BODY-MASS INDEX; RISK-FACTORS; SYMPTOMS; OBESITY; PREVALENCE; ESOPHAGITIS; ASSOCIATION; IMPACT; POWER; LINK;
D O I
10.1093/ije/dyaa082
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Background: Gastro-oesophageal reflux disease (GORD) is associated with multiple risk factors but determining causality is difficult. We used a genetic approach [Mendelian randomization (MRI)] to identify potential causal modifiable risk factors for GORD. Methods: We 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. Results: Observationally, 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. Conclusions: These 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.
引用
收藏
页码:1270 / 1281
页数:12
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