目的:在全表型关联研究(PheWAS)中探讨系统性硬化症胃肠道(GI)功能障碍的原因和原因,使用真实世界的临床记录数据。
方法:在英国皇家自由医院(RoyalFreeHospital,英国)对2,058名同意的系统性硬化症患者进行了有记录的临床评估,以进行详细的表型分析。诊断和药物被映射到结构化的术语字典(疾病本体论项目和DrugBank开放数据,分别)。PheWAS模型用于探索六个重要的SSc-GI域(便秘,腹泻,运动障碍,失禁,反流,和SIBO)以及接触各种合并症和药物。在报告UCLAGIT2.0问卷(GIT2.0)的定量GI症状评分的子队列中,确认并探索了PheWAS模型的“Hits”。
结果:1,546名个体进入PheWAS分析。在数据集中鉴定了673种不同的诊断和634种不同的药物,以及SSc特异性表型,例如抗核抗体(ANA)。Phewas分析揭示了药物之间的关联,诊断,和ANA有六个重要的SSc-GI结果:便秘,腹泻,运动障碍,失禁,反流,还有SIBO.随后,使用GIT2.0症状评分,证实了22种药物与SSc-GI的联系,四个诊断,三个ANA。
结论:使用无假设的Phewas方法,我们复制了已知的,揭示了潜在的小说,SSc-GI功能障碍的危险因素,包括阿片类药物,抗毒蕈碱,内皮素受体拮抗剂,和ANA子组。
To explore the causes of and contributors to gastrointestinal (GI) dysfunction in systemic sclerosis (SSc) in a phenome-wide association
study (PheWAS), using real-world clinical records data.
Twelve thousand five hundred thirty-five documented clinical assessments of 2058 consenting individuals with SSc at the Royal Free Hospital (UK) were available for detailed phenotyping. Diagnoses and drugs were mapped to structured dictionaries of terms (Disease Ontology project and DrugBank Open Data, respectively). A PheWAS model was used to explore links between 6 important SSc-GI domains (constipation, diarrhea, dysmotility, incontinence, gastroesophageal reflux, and small intestinal bacterial overgrowth [SIBO]) and exposure to various comorbidities and drugs. \"Hits\" from the PheWAS model were confirmed and explored in a subcohort reporting quantitative GI symptom scores from the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (GIT 2.0) questionnaire.
One thousand five hundred forty-six individuals were entered into the PheWAS analysis. Six hundred seventy-three distinct diagnoses and 634 distinct drugs were identified in the dataset, as well as SSc-specific phenotypes such as antinuclear antibodies (ANA). PheWAS analysis revealed associations between drugs, diagnoses, and ANAs with 6 important SSc-GI outcomes: constipation, diarrhea, dysmotility, incontinence, reflux, and SIBO. Subsequently, using GIT 2.0 symptom scores links with SSc-GI were confirmed for 22 drugs, 4 diagnoses, and 3 ANAs.
Using a hypothesis-free PheWAS approach, we replicated known, and revealed potential novel, risk factors for SSc-GI dysfunction, including drug classes such as opioid, antimuscarinic, and endothelin receptor antagonist, and ANA subgroup.