Table 4.
Putative drug target genes from GERD GWAS
| Gene | chr | Start, stop | Evidence for this particular gene | Drug(s) | Currently used for GERD/EA/BE | Highly expressed tissues(TPM) |
|---|---|---|---|---|---|---|
| CCKBR | 11 | 6,280,841–6,293,363 | Peak SNP rs12792379 is an eQTL for CCKBR | PROGLUMIDE, NETAZEPIDE | Yes | Stomach (40), brain frontal cortex (22), brain cortex (22), brain cerebellum (22), brain cerebellar hemisphere (22) |
| EPHB1 | 3 | 134,514,099–134,851,891 | Peak SNP rs60716777 is between EPHB1 and KY; this SNP is eQTL for KY, although noteworthy because EPHB1 is esophageal cancer drug target | VANDETANIB | Yes | Brain-cerebellar hemisphere (33), brain-cerebellum (23), brain-caudate (10), brain-putamen (9.5), cells-EBV (9.3) |
| CDK2 | 12 | 56,360,556–56,366,568 | See paragraph in discussion section | Multiple | Yes | EBV (64), esophagus-muscularis (32), lung (32), ovary (32), skin (28) |
| DPYD | 1 | 97,543,300–98,386,615 | Peak SNP rs7552188 is an eQTL (esophageal mucosa) for DPYD | ENILURACIL | No | Transformed fibroblasts (40), lung (27), whole blood (20), spleen (19), ovary (19) |
| PDE4B | 1 | 97,543,300–98,386,615 | Signal wholly over PDE4B; Significant MAGMA result | Multiple | No | Brain-spinal cord (29), brain-nucleus (17), brain-hypothalamus (14), brain-frontal (14), brain-cortex (14) |
| MST1R | 3 | 49,924,436–49,941,306 | Peak SNP rs7613875 is an eQTL (esophagus mucosa) for MST1R; significant MetaXcan and MAGMA result | NARNATUMAB, MK-8033, MGCD-265 | No | Brain-spinal cord (30), brain-nucleus (17), brain-substantia (16), brain-frontal (16), spleen (16) |
| LAMA2 | 6 | 129,204,286–129,837,710 | Signal wholly over LAMA2; Significant MAGMA result | OCRIPLASMIN | No | Ovary (121), nerve-tibial (91), fallopian tube (74), transformed fibroblasts (72), cervix-endocervix (55) |
Two further genes (KCNB2 on chromosome 8, SLC9A3 on chromosome 5) are drug targets, but we have not listed them in Table 4 as the link from the peak SNP to the putative target gene was weaker than for those in Table 4 (e.g., there are several equally likely candidate genes in the region). The top five expressed genes obtained from GTEx portal (https://gtexportal.org/home/gene, TPM is transcripts per kilobase million).