Principal Investigator: Professor Mauro D'Amato
BioDonostia Health Research Institute, Unit of Gastrointestinal Genetics, Paseo Dr. Beguiristain s/n, San Sebastian 20014. Spain.Tags: 30537, Functional dyspepsia, genetics, genome-wide association study
Lead Collaborators: Professor Mauro D’Amato
Collaborating Institutions and Addresses: Karolinska Institutet, Department of Medicine, Solna, Stockholm 17176. Sweden.
1a: Functional dyspepsia (FD) affects >10% of people worldwide with symptoms including postprandial fullness, early satiation and epigastric pain/burning in the absence of an underlying organic disease. FD etiology is uncertain with genetic factors playing a predisposing role, though no major large-scale effort has been undertaken. The project aims to study FD in relation to genotype, by exploiting UK Biobank GWAS resources for discovery purposes, and available case-control cohorts for replication (co-PI Prof Jan Tack, TARGID Leuven, BE). The results of this initiative will contribute to the identification of pathophysiological mechanisms, and hence ultimately provide novel therapeutic targets in FD.
1b: FD strongly impact patients’ QoL, and is associated with major substantial medical care costs. A high proportion of patients with severe and refractory GI symptoms also have psychosocial co-morbidities such as anxiety and depression, resulting in severely impaired daily functioning and work absenteeism. The development of therapeutic options is hampered by the heterogeneity of this symptom-based condition, and the limited understanding of the pathophysiological mechanisms. Hence, the potential for societal impact of FD-research aimed at identifying actionable disease pathways is extraordinary, and the long-term outcomes of this project are expected to positively impact the lives of many Europeans.
1c: Dyspepsia diagnoses will be identified using ICD10 codes from electronic medical records (current tally in UK Biobank, N approx 15000). Using a case-control study design, the prevalence of DNA variants in affected vs unaffected individuals will be compared in order to identify single nucleotide polymorphisms (SNPs) with significant effects on FD risk (genome wide association study – GWAS). Ad-hoc bioinformatic tools will be used to infer biology (mechanisms) from genetic information. An important asset of the proposal is a replication cohort of several hundred well-characterized FD patients and asymptomatic controls (Prof Tack), which will be key to replicate GWAS findings.
1d: In order to maximize statistical power, we plan to include data from all UK Biobank participants in the GWAS analyses.