Symptoms related with gastro-esophageal reflux disease (GERD) were previously shown to be linked with increased risk for the 2019 coronavirus disease (COVID-19). We aim to interrogate the possibility of a shared genetic basis between GERD and COVID-19 outcomes. Using published GWAS data for GERD (78 707 cases; 288 734 controls) and COVID-19 susceptibility (up to 32 494 cases; 1.5 million controls), we examined the genetic relationship between GERD and three COVID-19 outcomes: risk of developing severe COVID-19, COVID-19 hospitalization and overall COVID-19 risk. We estimated the genetic correlation between GERD and COVID-19 outcomes followed by Mendelian randomization (MR) analyses to assess genetic causality. Conditional analyses were conducted to examine whether known COVID-19 risk factors (obesity, smoking, type-II diabetes, coronary artery disease) can explain the relationship between GERD and COVID-19. We found small to moderate genetic correlations between GERD and COVID-19 outcomes (rg between 0.06 and 0.24). MR analyses revealed a OR of 1.15 (95% CI: 0.96–1.39) for severe COVID-19; 1.16 (1.01–1.34) for risk of COVID-19 hospitalization; 1.05 (0.97–1.13) for overall risk of COVID-19 per doubling of odds in developing GERD. The genetic correlation/associations between GERD and COVID-19 showed mild attenuation towards the null when obesity and smoking was adjusted for. Susceptibility for GERD and risk of COVID-19 hospitalization were genetically correlated, with MR findings supporting a potential causal role between the two. The genetic association between GERD and COVID-19 was partially attenuated when obesity is accounted for, consistent with obesity being a major risk factor for both diseases.

中文翻译：

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评估胃食管反流病与 COVID-19 感染风险之间的遗传关系

与胃食管反流病 (GERD) 相关的症状先前已被证明与 2019 年冠状病毒病 (COVID-19) 的风险增加有关。我们的目标是询问 GERD 和 COVID-19 结果之间共享遗传基础的可能性。使用已发布的 GERD（78 707 例；288 734 例对照）和 COVID-19 易感性（多达 32 494 例；150 万例对照）的 GWAS 数据，我们检查了 GERD 与三种 COVID-19 结果之间的遗传关系：发展为严重的风险COVID-19、COVID-19 住院和 COVID-19 总体风险。我们估计了 GERD 和 COVID-19 结果之间的遗传相关性，然后进行孟德尔随机化 (MR) 分析以评估遗传因果关系。进行条件分析以检查已知的 COVID-19 危险因素（肥胖、吸烟、II 型糖尿病、冠状动脉疾病）可以解释 GERD 和 COVID-19 之间的关系。我们发现 GERD 和 COVID-19 结果之间存在小到中度的遗传相关性（rg 在 0.06 和 0.24 之间）。MR 分析显示重症 COVID-19 的 OR 为 1.15（95% CI：0.96–1.39）；1.16 (1.01–1.34) COVID-19 住院风险；1.05 (0.97–1.13) 的 COVID-19 总体风险每增加一倍的发生 GERD 的几率。当调整肥胖和吸烟时，GERD 和 COVID-19 之间的遗传相关性/关联显示出对零的轻微衰减。GERD 的易感性和 COVID-19 住院的风险在遗传上相关，MR 发现支持两者之间的潜在因果关系。当考虑到肥胖时，GERD 和 COVID-19 之间的遗传关联被部分减弱，