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

Clinical Epigenetics

Table 2 Findings of individual-level allele score-based MR investigating causal effects of EAA on kidney function and CKD

Genetically predicted exposure	Model 1^a		Model 2^b
Genetically predicted exposure	Effect (95% CI)^c	P	Effect (95% CI)^c	P
eGFR^d
IEAA	− 0.001 (− 0.001, − 0.001)	< 0.001^f	− 0.001 (− 0.002, − 0.001)	< 0.001^f
GrimAA	− 0.001 (− 0.002, − 0.001)	< 0.001^f	− 0.001 (− 0.002, − 0.001)	< 0.001^f
HannumAA	− 0.0001 (− 0.001, 0.0004)	0.76	− 0.0002 (− 0.001, 0.0003)	0.44
PhenoAA	− 0.0002 (− 0.001, 0.0002)	0.3	− 0.0003 (− 0.001, 0.0002)	0.22
CKD^d
IEAA	1.02 (1.00, 1.04)	0.10	1.02 (1.00, 1.04)	0.07
GrimAA	1.02 (1.00, 1.04)	0.13	1.03 (1.00, 1.05)	0.02^e
HannumAA	1.00 (0.98, 1.02)	0.91	1.00 (0.98, 1.02)	0.99
PhenoAA	1.00 (0.98, 1.02)	0.78	1.00 (0.98, 1.02)	0.89

CI Confident interval; CKD Chronic kidney disease; eGFR Estimated glomerular filtration rate
^aAdjusted for age, sex, and 10 ancestry principal components
^bAdjusted for covariables in model 1 + hypertension, diabetes mellitus, lipid profiles, hypercholesterolemia, body mass index (BMI), and smoking
^cEffect sizes and CIs correspond to a 1 Z-score increase in EAA allele score (or genetically predicted EAA). Effect sizes are presented as beta estimates for log-transformed eGFR and hazard ratios for CKD
^deGFR is based on the combined cystatin C/creatinine-based estimation using CKD-EPI equation. CKD stage 3–5 is defined by eGFR < 60 ml/min per 1.73 m²
^eNominally significant
^fSignificant after FDR correction

ISSN: 1868-7083