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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
Source :
Neurogastroenterology & Motility; Jun2022, Vol. 34 Issue 6, p1-12, 12p
Publication Year :
2022

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
13501925
Volume :
34
Issue :
6
Database :
Complementary Index
Journal :
Neurogastroenterology & Motility
Publication Type :
Academic Journal
Accession number :
157112006
Full Text :
https://doi.org/10.1111/nmo.14236