ArticleGut2022
Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett's oesophagus and provides insights into clinical heterogeneity in reflux diagnosis.
Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 12 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
104 citing papers in PubMed, 12 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- Pooled it
- Gastrointestinal traits, common inflammatory disorders, gallstones, and biliary tract cancer: A network Mendelian randomization study.Journal of advanced research · 2026Pooled it
- Mapping Gastroesophageal Reflux Disease and Coronary Artery Disease: A Comprehensive Analysis of Multivariable Mendelian Randomization and Shared Genetic Etiology.Clinical cardiology · 2025Pooled it
- Causal Association Between Sedentary Behaviors and Health Outcomes: A Systematic Review and Meta-Analysis of Mendelian Randomization Studies.Sports medicine (Auckland, N.Z.) · 2024Pooled it
- Genetic correlation between smoking behavior and gastroesophageal reflux disease: insights from integrative multi-omics data.BMC genomics · 2024Pooled it
- Gastroesophageal reflux disease and non-alcoholic fatty liver disease: a two-sample Mendelian randomization combined with meta-analysis.Scientific reports · 2024Pooled it
- Gastroesophageal reflux disease and atrial fibrillation: a bidirectional Mendelian randomization study.International journal of medical sciences · 2024Pooled it
- Pooled it
- Causal relationship between gastroesophageal reflux disease, Barrett's esophagus, and epilepsy: A bidirectional Mendelian randomization study.Brain and behavior · 2023Pooled it
- The causal relationship between gastro-oesophageal reflux disease and idiopathic pulmonary fibrosis: a bidirectional two-sample Mendelian randomisation study.The European respiratory journal · 2023Pooled it
- Mendelian randomization study of gastroesophageal reflux disease and major depression.PloS one · 2023Pooled it
- A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer's disease and gastrointestinal tract disorders.Communications biology · 2022Pooled it
- Genetic causal association between kidney stones and proton pump inhibitors.International urology and nephrology · 2026Article
- Dissecting pleiotropy between major depressive disorder and physical disease comorbidities.Nature genetics · 2026Article
- Genetic Assessment of Oesophageal Safety of GLP-1 and GIP Receptor Perturbation: A Drug-Target Mendelian Randomisation Study.Biomedicines · 2026Article
- Barrett's esophagus-associated genetic loci in African Americans: a case-control study using the All of Us Research Program.European journal of gastroenterology & hepatology · 2026Observational
- Causal association between gastroesophageal reflux disease and anemia: Mendelian randomization analysis.Annals of medicine and surgery (2012) · 2026Article
- Gastroesophageal reflux disease and childhood asthma: A bidirectional two-sample Mendelian randomization study.Medicine · 2026Article
- Genetic evidence links alcohol, coffee, cheese, and anxiety to GERD risk: A Mendelian randomization study.Medicine · 2026Article
- Transformer-based InsightGWAS improves GERD genetic discovery via pretraining on GWAS for major depressive disorder.Communications biology · 2026Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 13 institutions in 5 countries.
Funding
Abstract
objectiveGastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett's oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications.
designWe applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA).
resultsWe identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA.
conclusionOur multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.