Two-stage study designs combining genome-wide association studies, tag single-nucleotide polymorphisms, and exome sequencing: accuracy of genetic effect estimates

Table 2 Bias in genetic effect estimates for a rare tag SNP and multiple rare causal SNPs

Trait	Gene	Population	Tag SNP						Rare SNP collapsing statistic r_i/n_i
			SNP	Significance level for additive test	Estimated power for additive test	Mean effect estimate			Correlation between tag SNP and r_i/ni	Mean effect estimate
						Over all data sets	Over data sets with significant tag effect	Relative bias (%)		Over all data sets	Over data sets with significant tag effect	Relative bias (%)
Q1	FLT4	Chinese	C5S5141	0.01	0.075	0.52	1.00	94	0.46	3.26	4.05	24
Q2	PLAT	Luhya	C8S1797	0.05	0.105	0.29	0.98	241	0.46	0.37	1.71	356
Q2	SREBF1	CEPH	C17S1023	0.05	0.135	0.59	1.63	177	0.81	2.00	3.97	98
Q2	VLDLR	Tuscan	C9S404	0.01	0.055	0.84	2.28	173	0.51	0.99	2.53	155
Q2	VLDLR	Tuscan	C9S471	0.01	0.055	0.84	2.28	173	0.51	0.99	2.53	155
Q2	VWF	CEPH	C12S193	0.01	0.070	0.34	0.93	171	0.65	0.61	1.12	85
Q2	VWF	CEPH	C12S200	0.01	0.080	0.41	1.15	182	0.61	0.57	1.04	84
Q2	VWF	CEPH	C12S203	0.05	0.075	0.21	0.53	157	0.48	0.63	0.93	47
Q2	VWF	CEPH	C12S211	0.01	0.070	0.34	0.87	152	0.78	0.65	1.39	113
Q2	VWF	Japanese	C12S193	0.05	0.070	0.21	0.72	244	0.56	-0.12	0.36	403
Q2	VWF	European	C12S193	0.05	0.200	0.31	0.79	153	0.62	0.55	1.03	87
Q2	VWF	European	C12S200	0.01	0.070	0.30	0.92	203	0.45	0.49	0.95	93
Q2	VWF	European	C12S203	0.05	0.070	0.18	0.50	180	0.46	0.58	0.85	47
Q2	VWF	European	C12S211	0.01	0.055	0.32	0.90	186	0.74	0.59	1.22	107
Q2	VWF	All	C12S203	0.05	0.140	0.16	0.41	160	0.48	0.69	1.06	54
DS	PTK2B	CEPH	C8S883	0.05	0.075	0.95	2.40	153	0.53	2.35	13.83	489
DS	PTK2B	Chinese	C8S885	0.05	0.050	0.16	1.24	692	0.87	0.38	2.68	610
DS	PTK2B	European	C8S911	0.05	0.130	0.63	1.27	102	0.50	2.04	2.86	40

Results for scenario 3. Values computed as described in the Results section. DS is disease status.

ISSN: 1753-6561