Evaluation of gene-based association tests for analyzing rare variants using Genetic Analysis Workshop 18 data

BMC Proceedings

Table 2 Empirical power for the 7 association tests using simulated phenotype data

Gene	Total # of rare variants	# of causal rare variants	Methods
			Linear W_L1	Linear W_Lp	Quadratic W_C	Quadratic W_H	Minimum W_min	Fisher's W_F	SKAT-O W_SKAT-O
*Outcome = SBP*
BTD	6	2	0.29	0.33	0.15	0.15	0.24	0.27	0.25
MAP4	8	4	0.96	0.93	0.96	0.91	0.97	0.99	0.96
ABTB1	6	0¹	0.05	0.05	0.16	0.09	0.12	0.12	0.08
PPP2R3A	8	2	0.25	0.18	0.21	0.13	0.28	0.32	0.19
GPR160	1	0¹	0.19	0.19	0.19	0.19	0.19	0.19	0.19
*Outcome = DBP*
BTD	5	2	0.36	0.35	0.16	0.11	0.29	0.31	0.26
MAP4	8	4	0.90	0.88	0.86	0.73	0.90	0.94	0.91
ABTB1	6	0¹	0.10	0.06	0.14	0.05	0.11	0.11	0.08
PPP2R3A	8	2	0.06	0.04	0.20	0.11	0.14	0.15	0.09
GPR160	1	0¹	0.27	0.27	027	0.27	0.27	0.27	0.27
*Outcome = hypertension status*
PDCD6IP	6	0¹	0.17	0.14	0.17	0.13	0.19	0.20	0.18
FLNB	13	4	0.07	0.07	0.10	0.11	0.08	0.11	0.08
SENP5	4	1	0.06	0.05	0.07	0.16	0.08	0.07	0.06

Two continuous phenotypes, systolic blood pressure (SBP) and diastolic blood pressure (DBP), and one binary phenotype, hypertension status, were analyzed. Rare variants (minor allele frequency ≤0.05) were grouped by gene and annotated as coding (strategy a in Table 1). All causal variants have the same direction of effect by the Genetic Analysis Workshop 18 simulation design. Level of tests was set to 0.05 because of a lack of power at a more stringent level. Genes presented are the ones with maximum power (bolded) among the 7 tests greater than 10% at the 0.05 level.
¹"Power" for these genes with no causal variants are attributable to linkage disequilibrium between non-causal rare variants in these genes and causal variants in other genes (see text for details).

ISSN: 1753-6561