Stepwise approach to SNP-set analysis illustrated with the Metabochip and colorectal cancer in Japanese Americans of the Multiethnic Cohort

Table 2 Association with colorectal cancer of individual TGF-β and WNT pathway SNPs

SNP	Gene	Minor allele frequency		Crude (unadjusted) association				Adjusted association^a
SNP	Gene	Cases	Controls	Odds ratio	95% CI	P value	FDR^c	Odds ratio	95% CI	P value	FDR
TGF-β pathway
rs17025857	TGFBR2	0.029	0.019	1.57	1.12, 2.21	0.009	0.48	2.01	1.28, 3.16	0.002	0.41
rs13075948	TGFBR2	0.026	0.018	1.49	1.04, 2.13	0.029	0.58	1.95	1.22, 3.11	0.005	0.44
rs11874392	SMAD7	0.375	0.342	1.16	1.03, 1.30	0.015	0.49	1.16	1.00, 1.34	0.049	1
rs3825977	SMAD3	0.453	0.490	0.86	0.77, 0.96	0.009	0.48	0.87	0.76, 1.01	0.063	1
rs4776890	SMAD3	0.206	0.234	0.85	0.74, 0.97	0.019	0.49	0.85	0.72, 1.01	0.059	1
rs4464148	SMAD7	0.038	0.053	0.70	0.53, 0.94	0.016	0.49	0.71	0.50, 1.01	0.057	1
rs11466531	TGFBR2	0.011	0.019	0.57	0.34, 0.97	0.034	0.59	0.71	0.39, 1.28	0.26	1
rs3773662	TGFBR2	0.011	0.020	0.56	0.33, 0.94	0.026	0.56	0.68	0.38, 1.23	0.20	1
WNT pathway
rs2439593	APC	0.0022	0.0003	6.39	1.53, 26.8	0.004	0.48	NA^b	NA	NA	NA
rs4944092	WNT11	0.156	0.129	1.24	1.07, 1.45	0.006	0.48	1.13	0.93, 1.38	0.22	1
rs11874392	SMAD7	0.375	0.342	1.16	1.03, 1.30	0.015	0.49	1.16	1.00, 1.34	0.049	1
rs4464148	SMAD7	0.038	0.053	0.70	0.53, 0.94	0.016	0.49	0.71	0.50, 1.01	0.057	1
rs11196187	TCF7L2	0.023	0.033	0.68	0.47, 0.99	0.042	0.60	0.69	0.43, 1.12	0.13	1

^aAdjusted for age, sex, BMI, height, smoking status, and the first five principal components among Japanese; odds ratios based on a linear genetic effect
^bNA: could not be estimated because of low frequency in controls
^cFDR: false discovery rate based on the 405 Metabochip SNPs that were in the selected pathways

ISSN: 1471-2164