Clinical Epigenetics

Table 3 Findings of summary-level MR investigating effects of eGFR on EAA

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

Outcome	Main analysis					Sensitivity analysis^a
Outcome	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 (eGFR_cr + eGFR_cys)^c
IEAA	133 SNPs	0.91	IVW	− 1.55 (− 3.50, 0.40)	0.12	119 SNPs	0.78	IVW	− 1.57 (− 3.66, 0.52)	0.14
HannumAA	133 SNPs	0.23	IVW	− 3.14 (− 5.23, − 1.05)	0.003^e	119 SNPs	0.24	IVW	− 2.78 (− 4.99, − 0.57)	0.01^e
GrimAA	133 SNPs	0.17	IVW	− 1.99 (− 3.94, − 0.04)	0.05^d	119 SNPs	0.40	IVW	− 1.79 (− 3.87, 0.28)	0.09
PhenoAA	133 SNPs	0.40	IVW	− 2.88 (− 5.21, − 0.54)	0.02^e	119 SNPs	0.73	IVW	− 2.83 (− 5.28, − 0.37)	0.02^e
eGFR (eGFR_cr + BUN)^c
IEAA	45 SNPs	0.98	IVW	− 2.08 (− 4.95, 0.79)	0.16	39 SNPs	0.83	IVW	− 1.99 (− 5.06, 1.07)	0.20
HannumAA	45 SNPs	0.35	IVW	− 3.24 (− 6.15, − 0.34)	0.03^d	39 SNPs	0.37	IVW	− 3.27 (− 6.43, − 0.11)	0.04^d
GrimAA	45 SNPs	0.53	IVW	− 1.31 (− 3.90, 1.29)	0.32	39 SNPs	0.52	IVW	− 1.53 (− 4.28, 1.22)	0.28
PhenoAA	45 SNPs	0.90	IVW	− 0.88 (− 4.29, 2.54)	0.62	39 SNPs	0.81	IVW	− 0.59 (− 4.24, 3.06)	0.75

BUN Blood urea nitrogen; CI Confident interval; eGFR Estimated glomerular filtration rate; SNP Single nucleotide polymorphism; IVW Inverse variance weighted
^aSensitivity analysis using genetic instruments derived from variants after excluding SNPs with relatively weak EAA associations and significant pleiotropic effects with known confounders
^bEffect sizes were from genetically predicted 1 unit increase in log-transformed eGFR to year in EAA
^cGenetic instrument for kidney function is developed from a GWAS for creatinine-based eGFR, with an additional filter to only keep SNPs that are associated with a second marker of kidney function (cystatin C-based eGFR or BUN) after Bonferroni correction
^dNominally significant
^eSignificant after FDR correction

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ISSN: 1868-7083

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