We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A survey of functional dyspepsia in 361,360 individuals: Phenotypic and genetic cross‐disease analyses.
- Authors
Garcia‐Etxebarria, Koldo; Carbone, Florencia; Teder‐Laving, Maris; Pandit, Anita; Holvoet, Lieselot; Thijs, Vincent; Lemmens, Robin; Bujanda, Luis; Franke, Andre; Zöllner, Sebastian; Boehnke, Michael; Zawistowski, Matthew; Esko, Tonu; Jan, Tack; D'Amato, Mauro
- Abstract
Background: Functional dyspepsia (FD) is a common gastrointestinal condition of poorly understood pathophysiology. While symptoms' overlap with other conditions may indicate common pathogenetic mechanisms, genetic predisposition is suspected but has not been adequately investigated. Methods: Using healthcare, questionnaire, and genetic data from three large population‐based biobanks (UK Biobank, EGCUT, and MGI), we surveyed FD comorbidities, heritability, and genetic correlations across a wide spectrum of conditions and traits in 10,078 cases and 351,282 non‐FD controls of European ancestry. Key Results: In UK Biobank, 281 diagnoses were detected at increased prevalence in FD, based on healthcare records. Among these, gastrointestinal conditions (OR = 4.0, p < 1.0 × 10−300), anxiety disorders (OR = 2.3, p < 1.4 × 10−27), ischemic heart disease (OR = 2.2, p < 2.3 × 10−76), and infectious and parasitic diseases (OR = 2.1, p = 1.5 × 10−73) showed strongest association with FD. Similar results were obtained in an analysis of self‐reported conditions and use of medications from questionnaire data. Based on a genome‐wide association meta‐analysis of genotypes across all cohorts, FD heritability was estimated close to 5% (hSNP2 = 0.047, p = 0.014). Genetic correlations indicate FD predisposition is shared with several other diseases and traits (rg > 0.344), mostly overlapping with those also enriched in FD patients. Suggestive (p < 5.0 × 10−6) association with FD risk was detected for 13 loci, with 2 showing nominal replication (p < 0.05) in an independent cohort of 192 FD patients. Conclusions & Inferences: FD has a weak heritable component that shows commonalities with multiple conditions across a wide spectrum of pathophysiological domains. This new knowledge contributes to a better understanding of FD etiology and may have implications for improving its treatment.
- Subjects
UNITED Kingdom; GENETIC correlations; PHENOTYPES; INDIGESTION; MYOCARDIAL ischemia; CORONARY disease; PARASITIC diseases; NEMATODE infections
- Publication
Neurogastroenterology & Motility, 2022, Vol 34, Issue 6, p1
- ISSN
1350-1925
- Publication type
Article
- DOI
10.1111/nmo.14236