Table 2.

Summary of Significant Associations Between Outcomes and Genotypes of SNPs in Candidate Genes.

Treatment	Outcome*	Locus	Marker	N (MM, mM, mm)	Effect Size (SE)¶	P-value†	MAF	Function
Combination	ΔFEV1%pred§	HSPA8	rs1461496	61 (24, 30, 7)	8.41 (2.62)	1.28x10−3	0.308	intron
	ACQ slope§	CHRM2	rs8191992	61 (18, 29, 14)	2.45x10−2 (6.26x10−3)	8.92x10−5‡	0.435	untranslated-3'
		CHRM2	rs6962027	61 (17, 28, 16)	2.52x10−2 (6.04x10−3)	2.98x10−5‡	0.431	near-gene-3'
		CHRM2	rs6967953	61 (17, 28, 16)	2.56x10−2 (6.11x10−3)	2.81x10−5‡	0.420	unknown
		ABCC1	rs119774	61 (52, 9, 0)	3.57x10−2 (1.36x10−2)	8.69x10−3	0.043	intron
Fluticasone	ΔFEV1%pred§	CRHR1	rs242941	64 (34, 26, 4)	−9.98 (3.24)	2.07x10−3	0.341	intron
		CRHR1	rs739645	63 (36, 19, 8)	1.03x101 (2.82)	2.61x10−4‡	0.156	intron
		CRHR1	rs1876831	64 (37, 19, 8)	1.04x101 (2.79)	1.89x10−4‡	0.159	intron
		CRHR1	rs1876829	63 (36, 19, 8)	1.03x101 (2.82)	2.62x10−4‡	0.156	intron
		CRHR1	rs1876828	64 (37, 19, 8)	1.04x101 (2.79)	1.89x10−4‡	0.154	intron
		HAL	rs17024981	64 (56, 8, 0)	2.15x101 (6.22)	5.46x10−4	0.078	intron
	ΔFEV1%pred||	COL2A1	rs2276458	64 (15, 37, 12)	−1.71x101 (6.00)	4.25x10−3	0.347	intron
		COL2A1	rs2276455	63 (17, 34, 12)	−1.71x101 (6.00 )	4.25x10−3	0.400	intron
		COL2A1	rs2276454	64 (17, 34, 13)	−1.71x101 (6.04)	4.61x10−3	0.412	coding-synon
Montelukast	ΔFEV1%pred§	CRHR1	rs739645	54 (34, 17, 3)	−6.26 (2.38)	8.61x10−3	0.156	intron
		CRHR1	rs1876831	54 (34, 16, 4)	−6.26 (2.38)	8.61x10−3	0.159	intron
		CRHR1	rs1876829	54 (34, 17, 3)	−6.26 (2.38)	8.61x10−3	0.156	intron
		CRHR1	rs1876828	53 (34, 16, 3)	−6.26 (2.38)	8.61x10−3	0.154	intron
		HDAC2	rs3757016	54 (17, 25, 12)	5.57 (2.12)	8.63x10−3	0.460	untranslated-3'
	ACQ slope§	CRHR1	rs242950	55 (10, 45, 0)	−3.54x10−2 (1.21x10−2)	3.57x10−3	0.126	intron

Abbreviations: MAF, minor allele frequency; N, number of patients; SE, Standard Error; synon, synonymous.

^*ΔFEV1%pred, change in percent predicted FEV1¹⁷ defined as (%predicted FEV1 (week 16) - %predicted FEV1 (enrollment) / %predicted FEV1 (enrollment)) × 100 (unit-less); ACQ slope, slope of the least squares regression line fit to a plot of Asthma Control Questionnaire¹⁶ score versus time at weeks 0, 2, 4, 8, 12, 16 (ACQ units / week). The ACQ score ranges from 0 to 6, with lower values indicating less-severe asthma and 0.5 unit as the minimal clinically important difference¹⁶.

^†P-values were determined from general linear models correcting for age, gender, height, and height² (see Methods). Reported p-values for each treatment – phenotype combination are for the maximum set of associated markers for which less than one false positive is predicted by the method of Storey and Tibshirani²³;

^‡associated markers that are significant by the Bonferroni multiple testing correction⁵⁷.

^§Additive model;

^||Recessive model.

^¶Effect size is calculated as the slope of the line between the adjusted means of the response variable for each genotype group.