Table 2 MR of the druggable genome identifies genes associated with aging phenotypes

Phenotype	MR method	Gene	Beta	SE	FDR-adjusted P value	PP.H4 (coloc SuSiE)
IEAA	Wald ratio	NHLRC1	−1.84	0.40	4.76 × 10⁻³	0.92
HannumAge	Wald ratio	NFKB1	−0.49	0.11	0.018	0.76
HannumAge	IVW	HDGF	−0.73	0.18	0.022	0.87
PhenoAge	Weighted median	TPMT	0.53	0.094	4.58 × 10⁻⁵	1.00
PhenoAge	IVW	LTBR	0.46	0.11	0.031	0.85
Multivariate longevity	Wald ratio	PSMA4	−0.065	0.007	1.23 × 10⁻¹⁹	0.93
	Weighted median	CASP8	0.028	0.006	6.40 × 10⁻⁴	1.00
	IVW	VDR	0.032	0.007	0.002	0.95
	Weighted median	VDR	0.032	0.008	0.012	0.95
	Wald ratio	WNT3	0.038	0.010	0.020	0.90
	Wald ratio	PTPN22	−0.022	0.006	0.027	0.94
	Wald ratio	CDC25A	0.048	0.013	0.036	0.82
	Wald ratio	CTSK	0.013	0.004	0.036	1.00

Results from our drug-target MR analysis of the druggable genome¹⁹ on five aging phenotypes. Genes significantly associated with an aging phenotype at a FDR of 0.05 and colocalized at PP.H4 > 0.75 are displayed. Standard errors are with respect to beta values. Statistical analyses were conducted using two-sided t-tests.
MR Mendelian randomization, FDR false discovery rate, IVW inverse variance weighted, IEAA intrinsic epigenetic age acceleration.

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