Table 1.
MR Analysis of LDL-C and Genetic Proxies for Lipid Therapy with Neuropsychiatric Adverse Effects and CAD
| Genetic Score | MR Method | Depression | Neuroticism | Insomnia | Coronary Artery Disease | ||||
|---|---|---|---|---|---|---|---|---|---|
| β (95% CI) |
P | β (95% CI) |
P | β (95% CI) |
P | β (95% CI) |
P | ||
| LDL-C | IVW | 0.008 (-0.02–0.03) |
.51 | -0.1 (-0.03–0.01) |
.37 | -0.01 (-0.06–0.04) |
.72 |
-0.44
(-0.53–-0.35) |
9.82E-22 |
| Weighted median | 0.001 | .99 | 0.002 (-0.03–0.003) |
.91 | -0.03 (-0.11–0.04) |
.39 |
-0.45s
(-0.53–-0.36) |
2.67E-25 | |
| MR-Eggera | 0.003 (-0.04–0.04) |
.99 | -0.001 (-0.002–0.002) |
.64 | -0.02 (-0.09–0.06) |
.66 |
-0.56
(-0.70–-0.41) |
4.76E-10 | |
| Interceptb | 0.0006 (-0.002–0.003) |
.64 | -0.001 (-0.002–0.002) |
.91 | 0.001 (-0.004–0.005) |
.78 | 0.009 (0.0003–0.02) |
.05 | |
| HMGCR | IVW |
0.11
(0.04–0.18) |
1.15E-03 | -0.1 (-0.18–-0.03) |
.008 | -0.13 (-0.33–0.07) |
.21 |
-0.43
(-0.62–-0.23) |
1.89E-05 |
| Weighted median |
0.11
(0.03–0.18) |
3.01E-03 | -0.1 (-0.18–-0.02) |
.02 | -0.13 (-0.34–0.08) |
.23 |
-0.42
(-0.63–-0.21) |
1.06E-04 | |
| MR-Eggera | 0.04 (-0.49–0.56) |
.92 | 0.1 (-0.31–0.5) |
.72 | -0.21 (-1.36–0.94) |
.78 | -0.76 (-1.84–0.33) |
.4 | |
| Interceptb | -0.005 (-0.03–0.04) |
.828 | -0.013 (-0.04–0.02) |
.5 | 0.005 (-0.07–0.08) |
.91 | 0.022 (-0.048–0.091) |
.65 | |
| NPC1L1 | IVW | 0.1 (-0.03–0.22) |
.12 | 0.02 (-0.15–0.11) |
.79 | -0.23 (-0.52–0.06) |
.11 |
-0.57
(-0.87–-0.26) |
2.58E-04 |
| Weighted median | 0.09 (-0.06–0.23) |
.23 | 0.02 (-0.17–0.13) |
.79 | -0.22 (-0.55–0.12) |
.21 |
-0.57
(-0.94–-0.21) |
2.16E-03 | |
| MR-Eggera | 0.07 (-0.58–0.72) |
.85 | -0.04 (-0.56–0.65) |
.91 | -0.15 (-1.59–1.3) |
.86 | 0.06 (-1.43–1.54) |
.95 | |
| Interceptb | 0.001 (-0.02–0.03) |
.939 | 0.002 (-0.03–0.02) |
.87 | -0.003 (-0.06–0.05) |
.92 | -0.024 (-0.079–0.031) |
.49 | |
| PCSK9 | IVW |
0.17
(0.09–0.26) |
2.61E-05 | 0.14 (-0.78–0.5) |
.75 | 0.02 (-0.1–0.13) |
.78 |
-0.37
(-0.59–-0.15) |
9.98E-04 |
| Weighted median |
0.16
(0.06–0.26) |
2.02E-03 | 0.03 (-0.12–0.06) |
.49 | 0.04 (-0.09–0.16) |
.54 |
-0.47
(-0.66–-0.27) |
3.36E-06 | |
| MR-Eggera | -0.3 (-1.05–0.46) |
.58 | 0.03 (-0.11–0.04)) |
.38 | 0.05 (-0.12–0.22) |
.61 | -0.56 (-0.86–-0.26) |
.07 | |
| Interceptb | 0.028 (-0.02–0.07) |
.433 | -0.006 (-0.03–0.04) |
.8 | -0.005 (-0.02–0.01) |
.62 | 0.019 (-0.005–0.04) |
0.25 | |
Abbreviations: CAD, coronary artery disease; IVW, inverse-variance weighted; LDL-C, low-density lipoprotein cholesterol; MR, Mendelian randomization; Q pval, P value.
Estimates are in log(odds ratio) for the effect of 1-SD increase in (LDL-C); all SNPs were oriented to the LDL-C decreasing allele.
Summary statistics are based on genome-wide association studies (GWAS) from Social Science Genetic Association Consortium (SSGAC) for depression and neuroticism [PMID: 27089181], from Hammerschlag et al. GWAS for insomnia [PMID: 28604731], and from the CARDIoGRAMplusC4D for CAD.
Multiple testing is correcting P value equal to (0.05/12=.0041). Significant P values are in bold.
aMR-Egger is considered a sensitivity test; insignificant P value does not contradict the conventional estimates from IVW.
bMR-Egger intercept is the average pleiotropic effect of genetic variants included in the analysis, if the value of the intercept is significantly different from zero, then the conventional MR estimate is biased (either presence of directional pleiotropy, violation of MR assumption, or both).