Table 2.
Mendelian randomization and genetic correlation analysis results of the effect of lower sclerostin levels on atherosclerosis and related risk factors*
| Exposure | Outcome | Model | N SNPs | OR | LCI | UCI | P |
|---|---|---|---|---|---|---|---|
| Lower sclerostin levels | Type 2 diabetes | Cis‐only MR | 5 | 1.32 | 1.03 | 1.69 | 0.030 |
| Lower sclerostin levels | Myocardial infarction | Cis‐only MR | 5 | 1.35 | 1.01 | 1.79 | 0.040 |
| Lower sclerostin levels | Coronary artery disease | Cis‐only MR | 5 | 1.01 | 0.74 | 1.39 | 0.954 |
| Lower sclerostin levels | Hypertension | Cis‐only MR | 5 | 1.02 | 0.98 | 1.06 | 0.311 |
| Lower sclerostin levels | Ischemic stroke | Cis‐only MR | 2 | 0.95 | 0.48 | 1.87 | 0.874 |
| Lower sclerostin levels | Cardioembolic stroke | Cis‐only MR | 2 | 0.88 | 0.23 | 3.35 | 0.849 |
| Lower sclerostin levels | Large vessel disease | Cis‐only MR | 2 | 0.88 | 0.21 | 3.75 | 0.866 |
| Lower sclerostin levels | Small vessel disease | Cis‐only MR | 2 | 0.57 | 0.13 | 2.60 | 0.470 |
| Exposure | Outcome | Model | N SNPs | β | SE | P |
|---|---|---|---|---|---|---|
| Lower sclerostin levels | Coronary artery calcification | Cis‐only MR | 5 | 0.236 | 0.110 | 0.033 |
| Lower sclerostin levels | Aortic calcification | Cis‐only MR | 5 | –0.051 | 0.273 | 0.851 |
| Lower sclerostin levels | Low density lipoprotein | Cis‐only MR | 5 | –0.008 | 0.044 | 0.857 |
| Lower sclerostin levels | High density lipoprotein | Cis‐only MR | 5 | –0.092 | 0.052 | 0.073 |
| Lower sclerostin levels | Triglyceride | Cis‐only MR | 5 | 0.107 | 0.082 | 0.190 |
| Lower sclerostin levels | Apolipoprotein A‐I | Cis‐only MR | 5 | –0.051 | 0.043 | 0.236 |
| Lower sclerostin levels | Apolipoprotein B | Cis‐only MR | 5 | 0.047 | 0.044 | 0.285 |
| Trait 1 | Trait 2 | Model | N SNPs | rg | SE_rg | P_rg |
|---|---|---|---|---|---|---|
| Lower sclerostin levels | Coronary artery calcification | Genetic correlation | All SNPs | 0.007 | 0.083 | 0.933 |
| Lower sclerostin levels | Hypertension | Genetic correlation | All SNPs | 0.134 | 0.045 | 3.10 × 10−3 |
| Lower sclerostin levels | Type 2 diabetes | Genetic correlation | All SNPs | –0.041 | 0.073 | 0.573 |
Model refers to which statistical method/model was applied. For cis‐only analysis, the inverse variance‐weighted Mendelian randomization (MR) method was used. N_SNPs means the number of genetic variants included as predictors for sclerostin. Estimate SE and P (and rg, SE_rg, P_rg) are the association estimates, SE, and P value of the MR (or the genetic correlation analysis). The odds ratio (OR) and 95% confidence interval of the MR estimates using cis‐acting variants, which refers to OR of disease risk per SD unit lowering of sclerostin levels, and is not applicable for the genetic correlation analysis. Importantly, the MR and genetic correlation analyses have different assumptions; therefore, the effect estimate is not directly comparable. We listed them in the same table to compare the direction of effects and the P value estimates across the 2 approaches. SNP = single‐nucleotide polymorphism; LCI = lower 95% confidence interval; UCI = upper 95% confidence interval.