Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases.
Jiyuan AnPuya GharahkhaniMatthew H LawJue-Sheng OngXikun HanCatherine M OlsenRachel E NealeJohn LaiTom L VaughanInes GockelRené ThiemeAnne C BöhmerJanusz JankowskiRebecca C FitzgeraldJohannes SchumacherClaire Pallesnull nullnull nullDavid C WhitemanStuart MacgregorPublished in: Nature communications (2019)
Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett's esophagus (BE) and esophageal adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 independent genome-wide significant loci for GERD. Several of the implicated genes are existing or putative drug targets. Loci discovery is greatest with a broad GERD definition (including cases defined by self-report or medication data). Further, 91% of the GERD risk-increasing alleles also increase BE and/or EA risk, greatly expanding gene discovery for these traits. Our results map genes for GERD and related traits and uncover potential new drug targets for these conditions.
Keyphrases
- genome wide
- gastroesophageal reflux disease
- dna methylation
- copy number
- systematic review
- small molecule
- randomized controlled trial
- high throughput
- genome wide association study
- adverse drug
- squamous cell carcinoma
- emergency department
- risk assessment
- deep learning
- human health
- big data
- data analysis
- locally advanced