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• W4377010350 abstract "In recent decades, upper gastrointestinal (GI) diseases have been highly prevalent worldwide. Although genome-wide association studies (GWASs) have identified thousands of susceptibility loci, only a few of them were conducted for chronic upper GI disorders, and most of them were underpowered and with small sample sizes. Additionally, for the known loci, only a tiny fraction of heritability can be explained and the underlying mechanisms and related genes remain unclear. In this study, we conducted a multi-trait analysis by the MTAG software and a two-stage transcriptome-wide association study (TWAS) with UTMOST and FUSION for seven upper GI diseases (oesophagitis, gastro-oesophageal reflux disease, other diseases of oesophagus, gastric ulcer, duodenal ulcer, gastritis and duodenitis and other diseases of stomach and duodenum) based on summary GWAS statistics from UK Biobank. In the MTAG analysis, we identified 7 loci associated with these upper GI diseases, including 3 novel ones at 4p12 (rs10029980), 12q13.13 (rs4759317) and 18p11.32 (rs4797954). In the TWAS analysis, we revealed 5 susceptibility genes in known loci and identified 12 novel potential susceptibility genes, including HOXC9 at 12q13.13. Further functional annotations and colocalization analysis indicated that rs4759317 (A>G) driven the association for GWAS signals and expression quantitative trait loci (eQTL) simultaneously at 12q13.13. The identified variant acted by decreasing the expression of HOXC9 to affect the risk of gastro-oesophageal reflux disease. This study provided insights into the genetic nature of upper GI diseases." @default.
• W4377010350 created "2023-05-19" @default.
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• W4377010350 date "2023-05-18" @default.
• W4377010350 modified "2023-10-16" @default.
• W4377010350 title "Systematic analyses of GWAS summary statistics from UK Biobank identified novel susceptibility loci and genes for upper gastrointestinal diseases" @default.
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• W4377010350 doi "https://doi.org/10.1038/s10038-023-01151-3" @default.
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• W4377010350 hasPublicationYear "2023" @default.
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