Leveraging the strong genetic correlation between GERD and related traits, we applied a multitrait GWAS model combining GWASs for body mass index (BMI), major depressive disorder (MDD), education attainment and GERD (and BE), to identify more susceptibility loci for GERD and BE (figure 1). The brief description for each input GWAS in the multitrait GWAS analysis and the equivalent effect sample size is shown in online supplemental table ST1. Candidate loci for GERD and BE achieving genome-wide significance (p<5e-8) were sent for replication in the independent 23andMe cohort (4 62 753 cases; 1 127 474 controls). Findings from these GWAS analyses were followed up with transcriptome-wide association studies (TWAS) and tissue enrichment analyses. TWAS analysis allows us to infer if there is a relationship between predicted gene-expression levels and GERD/BE risk. Tissue enrichment analyses allow us to assess whether the relevant GERD/BE-associated genes showed differential enrichment across 44 human tissues including oesophageal-related tissues. We finally applied a simple heuristic to dissect aetiological heterogeneity in GERD by separating GERD risk loci into obesity-driven and depression-driven categories; we then assessed these categories for differences in predicted gene expression in various tissues and for their ability to predict BE/EA susceptibility.