Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.
IBD Pharmacogenetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Int J Epidemiol. 2020 Aug 1;49(4):1270-1281. doi: 10.1093/ije/dyaa082.
Gastro-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.
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.
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.
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.
胃食管反流病（GORD）与多种危险因素相关，但确定因果关系较为困难。我们采用一种遗传方法[孟德尔随机化（MR）]来确定 GORD 的潜在可改变的因果风险因素。
我们使用来自英国生物库的 451097 名欧洲参与者的数据，使用医院定义的 ICD10 和 OPCS4 代码和自我报告数据（N=41024 例 GORD 病例）来定义 GORD。我们测试了 GORD 与 4 种肥胖指标[体重指数（BMI）、腰臀比（WHR）、代谢良好的更高体脂肪百分比和腰围]、吸烟状况、吸烟频率和咖啡因摄入量之间的观察性关联和基于 MR 的关联。
观察性研究表明，所有肥胖指标均与 GORD 的更高患病风险相关。吸烟和当前吸烟与 GORD 的更高患病风险相关。咖啡消费与 GORD 的更低患病风险相关，但在咖啡饮用者中，饮用更多含咖啡因的咖啡与 GORD 的更高患病风险相关。使用 MR，我们提供了强有力的证据表明，较高的 WHR 和 BMI 调整后的较高 WHR 导致 GORD。有较弱的证据表明，较高的 BMI、体脂肪百分比、咖啡饮用或吸烟导致 GORD，但仅对 BMI 和体脂肪百分比的观察效应可以排除。MR 估计的 WHR 效应相当于腰围每增加 5 厘米，GORD 的患病风险增加 1.23 倍。
这些结果提供了强有力的证据表明，较高的腰臀比导致 GORD。我们的研究表明，中心性脂肪分布对于导致 GORD 至关重要，而不是总体体重。
