Table 3.

Significant causal associations between epigenetic age acceleration and glaucoma endophenotypes estimated using bidirectional TSMR

Exposure	Outcome	SNPs	Method	Beta (95% CI)	P	PQ	PInt	PG	Power (%)
HannumAge	CCT	41	IVW	−0.85 (−1.57 to −0.14)	0.019	0.900	0.343	0.906	100
			MR-Egger	−1.65 (−3.43 to 0.13)	0.077
			MR-PRESSO	−0.85 (−1.46 to −0.24)	0.009
			WM	−0.86 (−1.89 to 0.17)	0.101
IEAA	CCT	55	IVW	−0.63 (−1.18 to −0.08)	0.024	0.694	0.781	0.693	100
			MR-Egger	−0.46 (−1.74 to 0.82)	0.480
			MR-PRESSO	−0.63 (−1.15 to −0.11)	0.021
			WM	−0.49 (−1.28 to 0.29)	0.218
PhenoAge	mRNFL	34	IVW	0.06 (0.01 to 0.11)	0.027	0.692	0.153	0.698	100
			MR-Egger	−0.02 (−0.13 to 0.10)	0.770
			MR-PRESSO	0.06 (0.01 to 0.11)	0.023
			WM	0.05 (−0.03 to 0.13)	0.200
GCP	IOP	30	IVW	−3.03 (−5.86 to −0.20)	0.036	0.210	0.417	0.200	100
			MR-Egger	−5.93 (−13.40 to 1.53)	0.130
			MR-PRESSO	−3.03 (−5.86 to −0.20)	0.044
			WM	−2.97 (−6.99 to 1.05)	0.147
PAI-1	IOP	36	IVW	0.0001 (0.00002 to 0.0002)	0.015	0.496	0.753	0.523	100
			MR-Egger	0.0001 (0.00001 to 0.0002)	0.042
			MR-PRESSO	0.0001 (0.00002 to 0.0002)	0.019
			WM	0.0001 (−0.00005 to 0.0002)	0.259
IOP	PAI-1	18	IVW	0.26 (0.01 to 0.50)	0.041	0.326	0.767	0.317	100
			MR-Egger	0.40 (−0.56 to 1.36)	0.429
			MR-PRESSO	0.26 (0.01 to 0.50)	0.057
			WM	0.20 (−0.14 to 0.53)	0.257

CCT, central corneal thickness; IOP, intraocular pressure; mRNFL, macular retinal nerve fiber layer thickness; PAI-1, DNAm-based plasminogen activator inhibitor-1 levels; GCP, DNAm-based granulocyte proportions; IEAA, intrinsic epigenetic age acceleration; TSMR, two-sample Mendelian randomization; IVW, inverse-variance weighted; MR-PRESSO, Mendelian randomization pleiotropy residual sum and outlier; WM, weighted median; OR, odds ratio; 95% CI, 95% confidence interval; P_Q was the P value derived from Cochran’s Q test using IVW method. P_Int was the P value derived from MR-Egger intercept. P_G was the P value derived from MR-PRESSO global test. P < 0.05 was considered as statistically significant