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, 10 (1), 4219

Gastroesophageal Reflux GWAS Identifies Risk Loci That Also Associate With Subsequent Severe Esophageal Diseases

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Gastroesophageal Reflux GWAS Identifies Risk Loci That Also Associate With Subsequent Severe Esophageal Diseases

Jiyuan An et al. Nat Commun.

Erratum in


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.

Conflict of interest statement

The authors declare no competing interests.


Fig. 1
Fig. 1
Genetic correlation between phenotypes. The lines with two arrows show the genetic correlation (standard error in brackets) from the result of LD-score regression rg, genetic correlation estimates from the LD score regression. There is sample overlap between UKBB cases with either ICD10, self-report or medicine based GERD and the numbers do not add up to the total UKBB samples size. As the correlation is computed as the estimated covariance divided by product of the estimated standard error of the two traits, the correlation estimates may be slightly >1 when the correlation is high. NA* sample size is too small to estimate rg
Fig. 2
Fig. 2
Manhattan plot for GERD from meta-analysis of 81,077 GERD cases and 307,284 controls. The x-axis shows genomic position (chromosome 1–22) and the y-axis shows the log10 (P-value) of the SNP association. The threshold for genome-wide significance is set at P = 5.0 × 10−8 (the red-dotted horizontal line)
Fig. 3
Fig. 3
Traits with significant genetic correlation with GERD. Vertical axis displays genetic correlation from LD-score regression. Error bars denote ±1 standard error

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