Table 7.

Gene region marginal and joint effects p-values for smoking initiation and CES-D, Sequence Kernel Association Testing, European ancestry (N=8086)

		CES-D	Smoking initiation (SI)
		Gene region p-value, SKAT	Gene region p-value, SKAT				G × E p-value, iSKAT (optimal test rho)
	Region location	Model 1	Model 1	Model 2	Model 3	Model 4	Model 5
NR3C1 (nSNP=211)	5q31.3	0.327	0.968	0.966	0.966	0.955	0.321 (1)
NR3C2 (nSNP =1147)	4q31.23	0.383	0.258	0.180	0.163	0.103	0.030 (0)
FKBP5 (nSNP =286)	6p21.31	0.007	0.017	0.019	0.019	0.028	0.545 (0)
CRHR1 (nSNP=1185)	17q21.31	0.336	0.927	0.894	0.892	0.809	0.161 (0.2)
		Smoking initiation	Depressive symptoms (CES-D)
		Gene region p-value, SKAT	Gene region p-value, SKAT				G × E p-value, iSKAT (optimal test rho)
	Region location	Model 1	Model 1	Model 2	Model 3	Model 4	Model 5
CHRNA5 (nSNP=107)	15q25.1	0.346	0.343	0.348	0.159	0.145	0.073 (0)
BDNF (nSNP=152)	11p14.1	0.598	0.281	0.244	0.180	0.248	0.760 (0)

Note. SKAT: Sequence Kernel Association Testing; iSKAT: interaction SKAT; G × E: Gene by environment; CES-D: Center for Epidemiological Studies-Depression 8 item scale. We weighted variants using the default β(1,25) weighting scheme to up-weight minor alleles. Optimal test rho: the value of rho to maximize statistical power resulting in the best linear combination of SKAT and burden tests. rho=1 is equivalent to a burden test while rho=0 is equivalent to a SKAT test. Bonferroni-adjusted alpha level for SI results: *p<0.003. Bonferroni-adjusted alpha level for CES-D results: *p<0.006.

M1: CES-D/SI = GENE + PCS

M2: SI/CES-D = GENE + CES-D/SMOKE + PCS

M3: SI/CES-D = GENE + CES-D/SMOKE + PCS + AGE + GED/HS + COHORT

M4: SI/CES-D = GENE + FEMALE + CES-D/SMOKE + PCS + AGE + GED/HS + COHORT

M5: SI/CES-D = GENE + FEMALE + FEMALE × GENE + CES-D/SMOKE + PCS + AGE + GED/HS + COHORT