Table 1
Information of 6 pleiotropic loci identified.
| GENOMIC LOCUS | UNIQID | CHR | START | END | LEAD SNPS | P–VALUE | MAPPED GENES | PP H4 |
|---|---|---|---|---|---|---|---|---|
| 6q25.3 | 6:160499565:C:T | 6 | 160067581 | 160929904 | rs2297362 | 3.32E–08 | IGF2R | 0.282 |
| 8p21.3 | 8:19942908:A:C | 8 | 19774890 | 19956346 | rs11986461 | 2.37E–08 | AC100802.3 | 0.590 |
| 8q24.13 | 8:126500031:C:G | 8 | 126435663 | 126533955 | rs28601761 | 1.83E–18 | RP11–136O12.2 | 0.983 |
| 19p13.11 | 19:19379549:C:T | 19 | 19260760 | 19865077 | rs58542926 | 2.87E–13 | TM6SF2 | 0.766 |
| 19q13.32 | 19:45415713:A:G | 19 | 45332635 | 45428234 | rs10414043 | 3.61E–13 | APOE, APOC1 | 0.854 |
| 22q13.31 | 22:44341986:C:T | 22 | 44323370 | 44411044 | rs2294917 | 2.90E–08 | PNPLA3 | 0.090 |
Figure 1
Manhattan diagram of pleiotropic loci between CAD and NAFLD.
Table 2
Gene set analysis results (top 10).
| GENE SET | N GENES | BETA | SE | P | PADJ |
|---|---|---|---|---|---|
| GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_MIGRATION | 144 | 0.320 | 0.075 | 1.02E–05 | 0.101 |
| PAL_PRMT5_TARGETS_UP | 186 | 0.248 | 0.061 | 2.35E–05 | 0.101 |
| GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION | 101 | 0.350 | 0.087 | 2.95E–05 | 0.101 |
| GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION | 407 | 0.174 | 0.044 | 3.56E–05 | 0.101 |
| GOBP_NOREPINEPHRINE_UPTAKE | 8 | 1.448 | 0.365 | 3.74E–05 | 0.101 |
| GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION | 216 | 0.236 | 0.061 | 5.05E–05 | 0.101 |
| PID_ANGIOPOIETIN_RECEPTOR_PATHWAY | 46 | 0.479 | 0.123 | 5.19E–05 | 0.101 |
| GOBP_NEGATIVE_REGULATION_OF_MUSCLE_ADAPTATION | 9 | 1.290 | 0.334 | 5.68E–05 | 0.101 |
| ZHAN_MULTIPLE_MYELOMA_CD1_DN | 42 | 0.518 | 0.138 | 8.82E–05 | 0.121 |
| GOBP_POSITIVE_REGULATION_OF_MONOCYTE_DIFFERENTIATION | 9 | 1.109 | 0.297 | 9.63E–05 | 0.125 |
Figure 2
Enrichment of pleiotropic genes in different tissues.
Figure 3
Pathway enrichment of pleiotropic eQTL genes (KEGG, wiki, GO).
Figure 4
Scatter plot and funnel plot of MR analysis. A: the scatter plot of the causal effect of CAD on NAFLD. B: the funnel plot of the causal effect of CAD on NAFLD. C: the scatter plot of the causal effect of NAFLD on CAD. D: the funnel plot of the causal effect of NAFLD on CAD.
Table 3
The results of MR analysis.
| EXPOSURE | OUTCOME | METHODS | ESTIMATE | P | HETEROGENEITY TEST | |
|---|---|---|---|---|---|---|
| ESTIMATE | P | |||||
| NAFLD | CAD | IVW (fixed) | 1.002 (0.937,1.071) | 0.964 | 3.254 | 0.071 |
| IVW (random) | 1.002 (0.888,1.13) | 0.980 | ||||
| DIVW | 1.002 (0.917,1.094) | 0.972 | ||||
| MR–RAPS | 1.002 (0.936,1.072) | 0.963 | ||||
| CAD | NAFLD | MR–RAPS | 0.999 (0.884,1.129) | 0.990 | 79.260 | 0.187 |
| IVW (fixed) | 0.999 (0.877,1.139) | 0.991 | ||||
| IVW (random) | 0.922 (0.697,1.218) | 0.562 | ||||
| MR–Egger (slope) | 0.007 (–0.013,0.027) | 0.512 | ||||
| MR–Egger (intercept) | 0.961 (0.741,1.245) | 0.761 | ||||
| Weighted mode | 1.001 (0.821,1.22) | 0.994 | ||||
| Weighted median | 0.999 (0.876,1.14) | 0.991 | ||||
| DIVW | 0.999 (0.883,1.131) | 0.990 | ||||
| MR–RAPS | 1.002 (0.937,1.071) | 0.964 | ||||