%0 Journal Article
%T A survey of functional dyspepsia in 361,360 individuals: Phenotypic and genetic cross-disease analyses.
%A Garcia-Etxebarria K
%A Carbone F
%A Teder-Laving M
%A Pandit A
%A Holvoet L
%A Thijs V
%A Lemmens R
%A Bujanda L
%A Franke A
%A Zöllner S
%A Boehnke M
%A Zawistowski M
%A Esko T
%A Jan T
%A D'Amato M
%J Neurogastroenterol Motil
%V 0
%N 0
%D Aug 2021 11
%M 34378841
%F 3.96
%R 10.1111/nmo.14236
%X 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.
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% ( h SNP 2 = 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: 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.