背景:肠易激综合征(IBS)是最常见的功能性消化系统疾病之一。我们对其合并症的理解,生物标志物,或长期风险仍不完整。
目的:确定IBS的合并症和生物标志物,并确定IBS对总体和导致特定死亡率的影响。
方法:我们分析了来自英国生物库(UKB)基于人群的队列的数据,其中有493,974名参与者,包括自我报告的医生诊断(n=20,603)和ICD-10诊断(n=7656)IBS患者,平均随访11年。我们进行了全表型关联研究(PheWAS)和竞争风险分析,以描述IBS患者的常见临床特征。
结果:在PheWAS分析中,在自我报告的医生诊断的IBS患者中,260个PheCode的比例明显过高,633例ICD-10诊断为IBS(ICD-10-IBS)的患者,221(40%)重叠。除了胃肠道疾病,精神病学,肌肉骨骼,和内分泌/代谢紊乱代表了IBS患者中最密切相关的PheCodes。自我报告的医生诊断的IBS与总死亡率增加无关,癌症死亡风险降低(风险比[HR]=0.78[95%CI=0.7-0.9])。最后,我们评估了IBS患者血清代谢物的变化,并将糖蛋白乙酰基(GlycA)确定为IBS的潜在生物标志物.GlycA的一个标准差增加使自我报告的IBS/ICD-10编码的风险增加了9%-20%(比值比[OR]=1.09[95%CI=1.1-1.1]/OR=1.20[95%CI=1.1-1.3]),ICD-10-IBS患者的总死亡率风险增加了28%(HR=1.28[95%CI=1.1-1.5])。
结论:我们的大规模关联研究确定IBS患者发生几种不同合并症的风险增加,并且在IBS患者中GlycA增加。
BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional digestive disorders. Our understanding about its comorbidities, biomarkers, or long-term risks is still incomplete.
OBJECTIVE: To characterize comorbidities and biomarkers for IBS and establish the effect of IBS on overall- and cause specific mortality.
METHODS: We analyzed data from the population-based cohort of the UK Biobank (UKB) with 493,974 participants, including self-reported physician-diagnosed (n = 20,603) and ICD-10 diagnosed (n = 7656) IBS patients, with a mean follow-up of 11 years. We performed a phenome-wide association study (PheWAS) and competing risk analysis to characterize common clinical features in IBS patients.
RESULTS: In PheWAS analyses, 260 PheCodes were significantly overrepresented in self-reported physician-diagnosed IBS patients, 633 in patients with ICD-10 diagnosed IBS (ICD-10-IBS), with 221 (40%) overlapping. In addition to gastrointestinal diseases, psychiatric, musculoskeletal, and endocrine/metabolic disorders represented the most strongly associated PheCodes in IBS patients. Self-reported physician-diagnosed IBS was not associated with increased overall mortality and the risk of death from cancer was decreased (hazard ratio [HR] = 0.78 [95% CI = 0.7-0.9]). Lastly, we evaluated changes in serum metabolites in IBS patients and identified glycoprotein acetyls (GlycA) as a potential biomarker in IBS. One standard deviation increase in GlycA raised the risk of self-reported IBS/ICD-10 coded by 9%-20% (odds ratio [OR] = 1.09 [95% CI = 1.1-1.1]/OR = 1.20 [95% CI = 1.1-1.3]) and the risk of overall mortality in ICD-10-IBS patients by 28% (HR = 1.28 [95% CI = 1.1-1.5]).
CONCLUSIONS: Our large-scale association study determined IBS patients having an increased risk of several different comorbidities and that GlycA was increased in IBS patients.