Table 3 Estimates of the effects of genetically predicted liver enzymes ALT, ALP and GGT (per 100% changes in concentration)¹⁸ on glycemic traits^17,23 using Mendelian randomization with different methodological approaches with and without potentially pleiotropic SNPs.

From: Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

Liver enzyme	Glycemic Traits	All SNPs						Excluding potentially pleiotropic SNPs related to obesity or another liver enzymes^‡
		SNPs	Method	Beta	95%CI	MR-Egger^§		SNPs	Method	Beta	95%CI	MR-Egger^§
		SNPs	Method	Beta	95%CI	Intercept	Intercept p value	SNPs	Method	Beta	95%CI	Intercept	Intercept p value
ALT	HbA1c (%)	4	IVW	0.006	−0.105 to 0.118	−0.003	0.765	3	IVW	0.03	−0.08 to 0.14	0.01	0.42
			MR-Egger	0.07	−1.02 to 1.15	—	—		MR-Egger	−0.14	−2.06 to 1.78	—	—
	Fasting glucose (mmol/L)	4	IVW	0.05	−0.06 to 0.17	−0.005	0.378	3	IVW	0.07	−0.05 to 0.19	−0.004	0.628
			MR-Egger	0.17	−0.07 to 0.41	—	—		MR-Egger	0.15	−0.77 to 1.08	—	—
	Insulin resistance	4	IVW	0.08	−0.04 to 0.21	−0.003	0.546	3	IVW	0.09	−0.04 to 0.22	−0.004	0.639
			MR-Egger	0.17	−0.09 to 0.43	—	—		MR-Egger	0.18	−0.60 to 0.96	—	—
	Beta cell function	4	IVW	−0.01	−0.12 to 0.09	−0.002	0.657	3	IVW	−0.02	−0.13 to 0.09	−0.004	0.552
			MR-Egger	0.03	−0.21 to 0.27	—	—		MR-Egger	0.08	−0.25 to 0.42	—	—
ALP	HbA1c (%)	14	IVW	−0.09	−0.15 to −0.02	0.001	0.636	13	IVW	−0.08	−0.15 to −0.01	0.003	0.222
			MR-Egger	−0.12	−0.30 to 0.05	—	—		MR-Egger	−0.156	−0.312 to 0.001	—	—
	Fasting glucose (mmol/L)	14	IVW	−0.12	−0.19 to −0.04	0.001	0.800	13	IVW	−0.12	−0.19 to −0.04	0.002	0.766
			MR-Egger	−0.14	−0.49 to 0.21	—	—		MR-Egger	−0.15	−0.52 to 0.23	—	—
	Insulin resistance	14	IVW	−0.09	−0.17 to −0.01	−0.001	0.827	13	IVW	−0.09	−0.17 to −0.01	−0.001	0.781
			MR-Egger	−0.06	−0.31 to 0.20	—	—		MR-Egger	−0.05	−0.33 to 0.23	—	—
	Beta cell function	14	IVW	−0.004	−0.068 to 0.061	−0.002	0.537	13	IVW	−0.004	−0.069 to 0.061	−0.002	0.521
			MR-Egger	0.05	−0.17 to 0.27	—	—		MR-Egger	0.06	−0.18 to 0.29	—	—
GGT	HbA1c (%)	26	IVW	−0.01	−0.04 to 0.03	−0.003	0.152	24	IVW	−0.002	−0.035 to 0.032	−0.002	0.279
			WM	0.02	−0.03 to 0.07	—	—		WM	0.02	−0.03 to 0.07	—	—
	Fasting glucose (mmol/L)	26	IVW	−0.01	−0.05 to 0.02	−0.01	0.11	24	IVW	−0.001	−0.038 to 0.036	−0.003	0.253
			WM	0.03	−0.02 to 0.08	—	—		WM	0.03	−0.02 to 0.09	—	—
	Insulin resistance	26	IVW	−0.02	−0.06 to 0.02	−0.003	0.331	24	IVW	−0.01	−0.05 to 0.03	0.00	0.97
			WM	−0.03	−0.08 to 0.03	—	—		WM	−0.03	−0.08 to 0.03	—	—
	Beta cell function	26	IVW	−0.01	−0.04 to 0.02	0.001	0.696	24	IVW	−0.005	−0.038 to 0.028	0.001	0.454
			WM	−0.04	−0.10 to 0.01	—	—		WM	−0.04	−0.08 to 0.01	—	—

IVW: Inverse Variance Weighted; WM: Weighted Median.
^‡Excluding SNP (rs2954021 (TRIB1)) for ALT and ALP, excluding glycemic traits related SNPs for GGT: rs516246 (FUT2) and rs1260326 (C2orf16, GCKR).
^§The intercept can be interpreted as an estimate of the average pleiotropic effect across the genetic variants where a corresponding p-value of <0.05 indicates the presence of directional pleiotropy across the genetic variants included in the analyses.

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Table 3 Estimates of the effects of genetically predicted liver enzymes ALT, ALP and GGT (per 100% changes in concentration)¹⁸ on glycemic traits^17,23 using Mendelian randomization with different methodological approaches with and without potentially pleiotropic SNPs.

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