Table 1.

Associations between genetically instrumented systemic iron status and type 2 diabetes without body mass index adjustment using the 3 single-nucleotide variations associated with all 4 iron biomarkers^a

	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	1.07	1.02-1.12	1.07	1.00-1.15	1.08	1.00-1.17	1.07	1.01-1.14	1.29	1.07-1.56	0.88 (.35)	–0.04 (.30)	0.06	1	2.64e-04
Ferritin	1.19	1.08-1.32	1.19	1.08-1.31	1.23	1.06-1.43	1.21	1.07-1.36	1.29	1.07-1.55	0.81 (.37)	–0.01 (.51)	0.125	1	1.71e-04
Transferrin saturation	1.06	1.02-1.09	1.06	1.02-1.10	1.07	1.02-1.12	1.07	1.03-1.11	1.10	1.03-1.19	0.59 (.44)	–0.01 (.41)	0.04	1	2.25e-04
Transferrin	0.91	0.87-0.96	0.91	0.90-0.93	0.92	0.83-1.01	0.91	0.87-0.96	0.91	0.86-0.97	0.33 (.56)	0.00 (.99)	–0.138	1	1.42e-04

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 the DIAGRAM consortium; genetic instruments were selected based on the GIS consortium study (n = 48 972).

^b SNVs rs1800562, rs1799945, and rs855791 associated with all 4 iron status biomarkers at genome-wide significance (P < 5 × 10⁻⁸) were used as genetic predictors for systemic iron status.

^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.