Table 3. Causal estimates for type 2 diabetes and glycemic traits using Mendelian randomization analysis.
| Instrumental variable | Alleles (effect/other) | Mendelian randomization analysis | |||
|---|---|---|---|---|---|
| Method | Causal estimate (95%CI) | P value | Heterogeneity P value | ||
| Incidence of Type 2 diabetes, PREVEND | Per 1-SD log | ||||
| rs6742078 | T/G | Wald-type | 0.58 (0.39 to 0.84)* | 0.005 | - |
| 2SLS | 0.56 (0.38 to 0.81)* | 0.002 | - | ||
| MGMM | 0.50 (0.27 to 0.92)* | 0.027 | - | ||
| rs4149056 | C/T | MGMM | 0.58 (0.05 to 6.08) * | 0.65 | - |
| rs16928809 | A/G | MGMM | 0.17 (0.02 to 2.16) * | 0.17 | - |
| Genetic risk score | - | MGMM | 0.34 (0.15 to 0.77) * | 0.009 | - |
| Type 2 diabetes, DIAGRAM (28) † | Per 1-unit log (umol/L) | ||||
| rs6742078 | T/G | summary statistics | 1.14 (0.96 to 1.35) * | 0.13 | - |
| rs4149056 | C/T | summary statistics | 0.67 (0.28 to 1.62) * | 0.38 | - |
| rs16928809 | A/G | summary statistics | 0.44 (0.15 to 1.35) * | 0.15 | - |
| Genetic risk score | - | summary statistics | 1.09 (0.93 to 1.29) * | 0.28 | 0.14 |
| Glucose, MAGIC (29) | Per 1-unit log (umol/L) | ||||
| rs6742078 | T/G | summary statistics | −0.04 (−0.07 to −0.01) ‡ | 0.02 | - |
| rs4149056 | C/T | summary statistics | 0.01 (−0.19 to 0.20) ‡ | 0.95 | - |
| rs16928809 | A/G | summary statistics | −0.05 (−0.28 to 0.18) ‡ | 0.67 | - |
| Genetic risk score | - | summary statistics | −0.04 (−0.07 to −0.01) ‡ | 0.02 | 0.89 |
| Insulin, MAGIC (29) | Per 1-unit log (umol/L) | ||||
| rs6742078 | T/G | summary statistics | −0.04 (−0.07 to −0.00) ‡ | 0.03 | - |
| rs4149056 | C/T | summary statistics | 0.12 (−0.08 to 0.32) ‡ | 0.25 | - |
| rs16928809 | A/G | summary statistics | −0.04 (−0.27 to 0.20) ‡ | 0.76 | - |
| Genetic risk score | - | summary statistics | −0.03 (−0.07 to −0.00) ‡ | 0.05 | 0.33 |
| HOMA-IR, MAGIC (29) | Per 1-unit log (umol/L) | ||||
| rs6742078 | T/G | summary statistics | −0.04 (−0.08 to −0.00) ‡ | 0.03 | - |
| rs4149056 | C/T | summary statistics | 0.08 (−0.13 to 0.28) ‡ | 0.47 | - |
| rs16928809 | A/G | summary statistics | −0.06 (−0.31 to 0.19) ‡ | 0.63 | - |
| Genetic risk score | − | summary statistics | −0.04 (−0.07 to −0.00) ‡ | 0.04 | 0.55 |
The bilirubin genetic risk score consisted of rs6742078 plus two other bilirubin SNPs in SLCO1B1, rs4149056 and in SLC22A18, rs16928809 (17; 27-29).
*
The causal ORs for T2D were estimated using the Wald type method, the two-stage least squares (2SLS) method, the multiplicative generalized method of moments (MGMM) and the summary statistics (27; 28). The causal OR for T2D was calculated as OR=exp(βIV).
†
The DIAGRAM GWAS includes both prevalent and incident cases of type 2 diabetes.
‡
The causal β coefficient (95%CI) for glucose (mmol/L), insulin and HOMA-IR was estimated for each SNP separately and the genetic risk score which is based on the combination of these three SNPs.