神经质增加胃食管反流病风险：来自双向孟德尔随机化的证据。

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中文摘要

背景： 胃食管反流病（GERD）是一种常见的胃肠道疾病，严重降低生活质量。新出现的数据表明，神经质——一种与应激反应性增加和对生理感觉敏感性增强相关的人格特质——可能促进GERD易感性。然而，因果关系仍不清楚。方法：进行了一项双向孟德尔随机化（MR）研究，以评估神经质与GERD之间的因果联系。神经质的遗传数据来源于英国生物银行的全基因组关联研究（GWAS）（n = 380,506），而GERD相关遗传数据来自FinnGen项目（n = 417,314）用于主要分析，并来自IEU Open GWAS数据库（n = 602,604）用于重复验证和荟萃分析。进行了敏感性分析，包括异质性和多效性检验，以评估因果推断的稳健性。结果：逆方差加权（IVW）分析显示，某些神经质特质与GERD风险增加之间存在显著关联。关联最强的特质是情绪（比值比[OR] = 2.01，95%置信区间[CI] = 1.60, 2.53，P = 1.5 × 10-9）、担忧（OR = 1.59，95% CI = 1.21, 2.07，P = .00078）和紧张（OR = 1.70，95% CI = 1.18, 2.44，P = .004）。加权中位数和MR-Egger回归敏感性分析支持这些发现。结果在重复验证和荟萃分析中得到验证。反向MR提示GERD可能影响“担忧”和“厌烦”等特质；然而，这些关联在Bonferroni校正后不显著。结论：神经质特质，包括情绪、担忧和紧张，可能与GERD风险增加相关。这些发现强调了心理特征在GERD发展中的潜在作用，并可能为GERD未来的风险评估和管理策略提供见解。

英文摘要

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder that severely reduces quality of life. Emerging data suggest that neuroticism, a personality trait associated with increased stress reactivity and sensitivity to physiological sensations, may contribute to GERD susceptibility. However, the causality remains unknown. A bidirectional Mendelian Randomization (MR) study was conducted to evaluate the causal link between neuroticism and GERD. Genetic data for neuroticism were sourced from the UK Biobank's genome-wide association study (GWAS) (n = 3,80,506), while GERD-associated genetic data were obtained from the FinnGen project (n = 4,17,314) for primary analysis and from the IEU Open GWAS database (n = 6,02,604) for replication and meta-analysis. Sensitivity analyses, including tests for heterogeneity and pleiotropy, were conducted to assess the robustness of causal inferences. Inverse-variance weighted (IVW) analyses revealed significant associations between certain neuroticism traits and an increased risk of GERD. The traits with the strongest associations were mood (odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.60, 2.53, P = 1.5 × 10-9), worry (OR = 1.59, 95% CI = 1.21, 2.07, P = .00078), and tense (OR = 1.70, 95% CI = 1.18, 2.44, P = .004). Weighted median and MR-Egger regression sensitivity analyses supported these findings. The results were validated in replication and meta-analysis. Reverse MR suggested GERD might influence traits like "WORRY" and "FED-UP"; however, these associations were non-significant after Bonferroni correction. Neuroticism traits, including mood, worry, and tense, may be associated with an increased risk of GERD. These findings highlight the potential role of psychological characteristics in GERD development and may provide insights into future risk assessment and management strategies for GERD.