Table 3.
MR-link results using GTEx liver eQTLs.
| Gene name | Causal effect | p Value | #IVs | Biological function and link to LDL-C |
|---|---|---|---|---|
| PVRL2 | 0.3177 | 3.0E−14 | 1 | Poliovirus receptor-related 2 (PVRL2) is a protein-coding gene also known as NECTIN2. It is a cell-membrane protein located in the LDL-C GWAS locus APOE. siRNA experiments show that LDL-C uptake is increased in cells upon its downregulation48. PVRL2 knockout mice also had less atherosclerosis46. Both studies indicate a reduction in LDL-C upon downregulation of PVRL2. |
| PSRC1 | −0.0847 | 3.99E−09 | 1 | Proline and serine rich coiled-coil 1 (PSRC1) is a protein-coding gene located in an LDL-C GWAS locus35. PSRC1 has not been found to have an effect on cholesterol despite being targeted in a specific functional study43. The IV for PSRC1 is overlapping with the IV for CELSR2 and SORT1. |
| SORT1 | −0.0865 | 5.89E−09 | 1 | Sortilin (SORT1) is a protein-coding gene located in an LDL-C GWAS locus35. siRNA and knockdown experiments have functionally validated that SORT1 has a negative effect on LDL-C levels41,42. The IV for SORT1 is overlapping with the IV for PSRC1 and CELSR2. |
| CELSR2 | −0.0993 | 6.8E−08 | 1 | Cadherin EGF LAG Seven-Pass G-Type Receptor 2 (CELSR2) is a protein-coding gene located in an LDL-C GWAS locus35. CELSR2 has not been found to have an effect on cholesterol despite being targeted by a specific functional study43. The IV for CELSR2 is overlapping with the IV for PSRC1 and SORT1. |
This table lists four Bonferroni-significant genes that were identified using GTEx liver eQTLs. Gene names are according to ENSEMBL GENES 96 database (human Genome build 37). The causal effect estimate represents changes in LDL-C (mg per dL) per standard deviation increase in gene expression. p Values listed in this table are not adjusted for multiple testing (MR-link calibrated two-sided p values, see Supplementary Note 1). Full summary statistics of these genes are shown in Supplementary Table 2. LDL-C low-density lipoprotein cholesterol, GWAS genome-wide association study, siRNA small interfering RNA, IV instrumental variable.