Table 3. Multivariable Mendelian randomization estimates for effects of genetically mimicked statins (effect sizes of LDL-cholesterol) and of testosterone (effect size) together on IHD in men and women using the UK Biobank.
| Mendelian randomization estimates | ||||||||
|---|---|---|---|---|---|---|---|---|
| Sex | Exposures | Instrumented by | Adjusted for | Method | OR | 95% CI | P value | MR-Egger intercept p-value |
| Men | Statin mimic | 1 Statin SNP on LDL-cholesterol | Testosterone | Inverse variance weighted | 1.05 | 0.74 to 1.47 | 0.79 | |
| Testosterone | 125 SNPs on testosterone | statin | Inverse variance weighted | 1.11 | 1.04 to 1.20 | 0.003 | ||
| Statin mimic | 1 Statin SNP on LDL-cholesterol | Testosterone | MR-Egger | 0.73 | 0.48 to 1.11 | 0.14 | ||
| Testosterone | 125 SNPs on testosterone | statin | MR-Egger | 1.09 | 1.02 to 1.17 | 0.02 | 0.005 | |
| Statin mimic | 6 Statin SNPs on LDL-cholesterol | Testosterone | Inverse variance weighted | 1.02 | 0.72 to 1.43 | 0.91 | ||
| Testosterone | 125 SNPs on testosterone | statin | Inverse variance weighted | 1.11 | 1.04 to 1.20 | 0.003 | ||
| Women | Statin mimic | 1 Statin SNP on LDL-cholesterol | Testosterone | Inverse variance weighted | 0.98 | 0.75 to 1.16 | 0.53 | |
| Testosterone | 254 SNPs on testosterone | statin | Inverse variance weighted | 0.96 | 0.90 to 1.04 | 0.33 | ||
| Statin mimic | 1 Statin SNP on LDL-cholesterol | Testosterone | MR-Egger | 0.72 | 0.55 to 0.94 | 0.02 | ||
| Testosterone | 254 SNPs on testosterone | statin | MR-Egger | 0.96 | 0.89 to 1.03 | 0.27 | 0.001 | |
| Statin mimic | 6 Statin SNPs on LDL-cholesterol | Testosterone | Inverse variance weighted | 0.92 | 0.74 to 1.16 | 0.49 | ||
| Testosterone | 254 SNPs on testosterone | statin | Inverse variance weighted | 0.97 | 0.90 to 1.04 | 0.36 | ||
One statin SNP is rs12916, and six statin SNPs additionally included rs5909, rs10066707, rs17238484, rs2006760 and rs2303152 taking into account all their correlations. The unit of LDL-cholesterol is approximately 0.83 mm/L. An effect size of testosterone is approximately, 0.23 nmol/L in women (Haring et al., 2012) and 3.1 nmol/L in men (Mohr et al., 2005).