Table 4. Mendelian randomization inverse variance weighted estimates for genetically mimicked effects of the anti-inflammatory anakinra raising IL-1Ra (effect size) (Swerdlow et al., 2012) on testosterone (effect size) and ischemic heart disease and for genetically mimicked effects of tocilizumab raising serum IL-6r (ng/ml) (Rafiq et al., 2007) on testosterone in men and women using the UK Biobank .
| Therapy | Target | Outcome | # SNPs | Measure | Estimate | 95% CI | p-value | |
|---|---|---|---|---|---|---|---|---|
| Men | Anakinra | IL-1Ra | testosterone | 2 | beta | 0.022 | 0.01 to 0.04 | 0.002 |
| IHD | 2 | OR | 1.08 | 1.01 to 1.15 | 0.017 | |||
| Tocilizumab | IL-6r | testosterone | 1 | beta | 0.003 | −0.06 to 0.13 | 0.96 | |
| Women | Anakinra | IL-1Ra | testosterone | 2 | beta | −0.01 | −0.04 to 0.01 | 0.24 |
| IHD | 2 | OR | 0.99 | 0.91 to 1.08 | 0.86 | |||
| Tocilizumab | IL-6r | testosterone | 1 | beta | 0.002 | −0.02 to 0.02 | 0.84 |
SNPs mimicking anakinra are rs6743376 and rs1542176.
The SNP mimicking tocilizumab is rs7529229.
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).