Comparing strategies for combined testing of rare and common variants in whole sequence and genome-wide genotype data

Table 1 Analysis of real data: real SBP and candidate gene AGTR1

SNP panel	Weight	Common SNPs		Rare SNPs		Joint tests
		MAF >5 %		MAF ≤5 %		Default	WS	Fisher
		N_SNP	p value	N_SNP	p value	p value	p value	p value
AGTR1 with no flanking region, positions 148415571–148460795
GWAS	equal	11	0.189	7	0.097	0.177	0.102	0.101
GWAS	1/ν	11	0.113	7	0.050	0.054	0.044	0.043
SEQ	equal	74	0.203	138	0.060	0.173	0.076	0.076
SEQ	1/ν	74	0.160	138	0.098	0.083	0.088	0.090
AGTR1 with 30 kb flanking region, positions 148385571–148490795
GWAS	equal	30	0.100	12	0.072	0.092	0.050	0.052
GWAS	1/ν	30	0.045	12	0.069	0.030	0.029	0.029
SEQ	equal	198	0.053	300	0.067	0.047	0.030	0.032
SEQ	1/ν	198	0.039	300	0.172	0.045	0.044	0.050
AGTR1 with 500 kb flanking region, positions 147915571–148960795
GWAS	equal	277	0.206	51	0.048	0.196	0.061	0.065
GWAS	1/ν	277	0.151	51	0.064	0.102	0.059	0.066
SEQ	equal	2170	0.192	2244	0.069	0.173	0.080	0.085
SEQ	1/ν	2170	0.157	2244	0.051	0.062	0.057	0.060
AGTR1 containing LD-block, positions 148344702–148568958
GWAS	equal	80	0.058	19	0.076	0.055	0.035	0.036
GWAS	1/ν	80	0.040	19	0.114	0.034	0.036	0.039
SEQ	equal	499	0.029	592	0.106	0.027	0.027	0.030
SEQ	1/ν	499	0.027	592	0.112	0.025	0.026	0.030

Association of AGTR1 with real SBP was tested with a linear kernel on minor allele dosage data for GWAS and sequence (SEQ); p ≤0.05 bold. N_SNP common and rare SNPs, respectively, were combined into joint tests: kernel K _all (default), weighted sum test (WS), and Fisher’s p value pooling for correlated p values

ISSN: 1753-6561