Table 1.

Pathways and gene sets significantly associated with renal cell carcinoma in the GWAS meta-analysis (P < 1.36 × 10⁻⁵)^a and UK Biobank (P<0.05)

			Discovery Set (GWAS Meta-Analysis; 10,784 cases and 20,406 controls		Replication Set (UK Biobank; 903 cases and 451,361 controls)
MSigDB Pathway / Gene Set	NGenes	NSNPs	P	Most Significant Genesb	P	Most Significant Genesb
Benporath cycling genes	612	26858	2.00 × 10−7	TIPIN, CDKN2C, CENPQ	0.016	FANCD2,RAN,ZC3HC1
Reactome AKT phosphorylates targets in the cytosol	12	402	6.50 × 19−7	AKT1, CASP9, CDKN1B	0.00018	CASP9,AKT1S1,AKT2
BioCarta RAS pathway	21	957	7.50 × 10−7	AKT1, CASP9, MAP2K1	0.0034	CASP9
Reactome PI3K/AKT activation	34	1557	8.50 × 10−7	AKT1, CASP9, IRS2	0.0060	CASP9
Fortschegger PHF8 targets up	247	14870	1.30 × 10−6	TIPIN, INSR, GRB10	0.013	IGF1R,ATF4,CTSC
Reactome PIP3 activates AKT signaling	25	1095	1.45 × 10−6	AKT1, CASP9, CDKN1B	0.0045	CASP9
West adrenocortical tumor dn	491	31986	2.25 × 10−6	RBPMS, IRF5, ZFP36L2	0.042	CASP9,RPL38,KCNK3
Reactome signaling by SCF-KIT	72	3976	5.10 × 10−6	AKT1, CASP9, MAP2K1	0.0074	CASP9,CDK1,SOCS1
Reactome GAB1 signalosome	34	1832	6.15 × 10−6	AKT1, CASP9, CDKN1B	0.0060	CASP9
KEGG prostate cancer	82	5107	6.25 × 10−6	AKT1, CASP9, MAP2K1	0.00046	CASP9,IGF1R,ATF4
BioCarta HDAC pathway	29	2284	6.45 × 10−6	AKT1, INSR, MEF2D	0.034	IGF1R
Reactome PI3K events in ERBB4 signaling	34	2757	7.05 × 10−6	AKT1, CASP9, CDKN1B	0.0060	CASP9
PID PI3KCI AKT pathway	33	1451	9.00 × 10−6	AKT1, CASP9, CDKN1B	0.00058	CASP9
Pujana CHEK2 PCC network	732	26725	9.50 × 10−6	POT1, CDKN2C, TFDP2	0.016	RAN,MIEF1,CENPA

^aPathways/gene sets statistically significant at Bonferroni-adjusted α-level of 1.36 × 10⁻⁵ (0.05/3678).

^bTop 3 gene-level test results with a P-value <0.001