Table 2.
Associations between genetically instrumented iron status and type 2 diabetes without body mass index adjustment using the separately selected single-nucleotide variations associated with each iron biomarkera
| IVW-fixed | IVW-random | Simple median | Weighted median | MR Egger | MRMixc | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Exposureb | OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | Q statistic (P) | Intercept (P) | θ | π0 | σ2 |
| Iron | 1.06 | 1.01-1.11 | 1.06 | 0.99-1.13 | 1.05 | 0.97-1.14 | 1.06 | 1.00-1.13 | 1.14 | 1.02-1.26 | 4.49 (.21) | –0.01 (.21) | 0.035 | 1 | 1.14e-04 |
| Ferritin | 1.06 | 0.98-1.15 | 1.06 | 0.83-1.36 | 1.08 | 0.95-1.24 | 1.17 | 1.05-1.31 | 1.45 | 0.96-2.21 | 25.16 (< .01) | –0.03 (.16) | 0.13 | 0.647 | 1.23e-03 |
| Transferrin saturation | 1.06 | 1.03-1.09 | 1.06 | 1.03-1.09 | 1.07 | 1.01-1.12 | 1.07 | 1.03-1.11 | 1.07 | 1.02-1.13 | 2.28 (.52) | –0.002 (.69) | 0.03 | 1 | 4.95e-05 |
| Transferrin | 0.95 | 0.92-0.97 | 0.95 | 0.89-1.00 | 0.88 | 0.79-0.97 | 0.97 | 0.93-1.00 | 0.98 | 0.90-1.05 | 30.42 (< .01) | –0.008 (.28) | –0.28 | 0.552 | 4.72e-03 |
Abbreviations: BMI, body mass index; DIAGRAM, DIAbetes Genetics Replication and Meta-analysis; GIS, Genetics of Iron Status; IVW, inverse variance weighted; MR, Mendelian randomization; MRMix, MR analysis using mixture-model; OR, odds ratio; SNV, single-nucleotide variation (formerly single-nucleotide polymorphism [SNP]); T2D, type 2 diabetes.
a Data source and sample size: T2D case-control (n = 74 124 and 824 006, respectively) study based on DIAGRAM consortium; genetic instruments were selected based on GIS consortium study (n = 48 972).
b SNVs associated with serum iron (rs1800562, rs1799945, rs855791, rs8177240, and rs7385804), Ferritin (rs1800562, rs1799945, rs855791, rs744653, rs651007, and rs411988), Transferrin saturation (rs1800562, rs1799945, rs855791, rs8177240, and rs7385804), and Transferrin (rs1800562, rs1799945, rs855791, rs744653, rs8177240, rs9990333, rs4921915, rs6486121, and rs174577) at genome-wide significance (P < 5 × 10−8) were used as genetic predictors for each iron biomarker.
c θ, the estimates of causal effects generated by MRMix approach; π0, the proportion of valid instrumental variables; and σ2, the unknown variance parameter associated with the invalid instrumental variables.