Maclean, Rory H;
Ahmed, Fiza;
Ong, Voon H;
Murray, Charles D;
Denton, Christopher P;
(2023)
Phenome-Wide Association Study of Drugs and Co-morbidities Associated with Gastrointestinal Dysfunction in Systemic Sclerosis.
The Journal of Rheumatology
, 50
(2)
, Article 220990. 10.3899/jrheum.220990.
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Abstract
OBJECTIVE: To explore the causes of and contributors to gastrointestinal (GI) dysfunction in systemic sclerosis in a Phenome-Wide Association Study (PheWAS), using real-world clinical records data. METHODS: 12,535 documented clinical assessments of 2,058 consented individuals with systemic sclerosis 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 six important SSc-GI domains (constipation, diarrhoea, dysmotility, incontinence, reflux, and SIBO) and exposure to various comorbidities and drugs. 'Hits' from the PheWAS model were confirmed and explored in a sub-cohort reporting quantitative GI symptom scores from the UCLA GIT 2.0 questionnaire (GIT 2.0). RESULTS: 1,546 individuals were entered into the PheWAS analysis. 673 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 six important SSc-GI outcomes: constipation, diarrhoea, dysmotility, incontinence, reflux, and SIBO. Subsequently, using GIT 2.0 symptom scores, links with SSc-GI were confirmed for 22 drugs, four diagnoses, and three ANAs. CONCLUSION: 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, anti-muscarinic, and endothelin receptor antagonist, and ANA subgroup.
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