Effects of epigenetic age acceleration on kidney function: a Mendelian randomization study

Clinical Epigenetics

Table 1 Findings of summary-level MR investigating effects of EAA on eGFR and CKD

Genetically predicted exposure	Main analysis					Sensitivity analysis^a
Genetically predicted exposure	Genetic instruments	Egger intercept P	Primary method	Effect (95% CI)^b	P	Genetic instruments	Egger intercept P	Primary method	Effect (95% CI)^b	P
eGFR
IEAA	36 SNPs	0.02	MR Egger	− 0.01 (− 0.02, − 0.002)	0.02^c	22 SNPs	0.07	MR Egger	− 0.01 (− 0.02, − 0.001)	0.03^c
HannumAA	22 SNPs	0.72	IVW	0.002 (− 0.005, 0.01)	0.52	19 SNPs	0.06	MR Egger	− 0.01 (− 0.02, 0.003)	0.20
GrimAA	4 SNPs	0.51	IVW	− 0.02 (− 0.05, 0.004)	0.09	3 SNPs	0.18	IVW	− 0.03 (− 0.06, − 0.005)	0.02^c
PhenoAA	13 SNPs	0.92	IVW	− 0.001 (− 0.01, 0.01)	0.86	9 SNPs	0.39	IVW	− 0.003 (− 0.01, 0.005)	0.45
CKD
IEAA	36 SNPs	0.05	MR Egger	1.24 (1.00, 1.54)	0.05	22 SNPs	0.04	MR Egger	1.29 (1.06, 1.58)	0.02^c
HannumAA	22 SNPs	0.10	IVW	0.93 (0.81, 1.06)	0.25	19 SNPs	0.15	IVW	0.95 (0.86, 1.06)	0.35
GrimAA	4 SNPs	0.33	IVW	1.18 (0.84, 1.67)	0.35	3 SNPs	0.55	IVW	1.36 (1.02, 1.80)	0.03^c
PhenoAA	13 SNPs	0.36	IVW	0.94 (0.81, 1.10)	0.46	9 SNPs	0.91	IVW	1.02 (0.87, 1.18)	0.84

CI Confident interval; CKD Chronic kidney disease; eGFR Estimated glomerular filtration rate; SNP Single nucleotide polymorphism; IVW Inverse variance weighted
^aSensitivity analysis using genetic instruments derived from a conservative set of variants after excluding SNPs with relatively weak EAA associations and strong associations with other phenotypes
^bEffect sizes and CIs correspond to a 5 year increase in genetically predicted EAA. Effect sizes are presented as beta estimates for log-transformed eGFR and hazard ratios for CKD
^cNominally significant

ISSN: 1868-7083