Table 1

Single nucleotide polymorphisms (SNPs) showing highest association signals for severe asthma

Chromosome	Locus	SNP	Position	AUGOSA (933 cases, 3346 controls)			AAGC (231 cases, 1345 controls)			Meta-analysis
Chromosome	Locus	SNP	Position	r²_imp	OR (95% CI)	p Value	r²_imp	OR (95% CI)	p Value	OR (95% CI)	p Value
Six genotyped SNPs from regions identified in genotyped SNP analyses
2	IL18R1	rs3771166	102352654	GENO	0.79 (0.71 to 0.88)	1.93×10⁽⁻⁵⁾	GENO	0.71 (0.57 to 0.87)	0.001	0.77 (0.70 to 0.85)	1.24×10⁽⁻⁷⁾
5	C5orf56	rs11745587	131824821	GENO	1.30 (1.17 to 1.45)	2.09×10⁽⁻⁶⁾	GENO	1.13 (0.92 to 1.39)	0.25	1.26 (1.15 to 1.39)	2.13×10⁽⁻⁶⁾
6	CD83	rs9382936	14173097	GENO	1.31 (1.17 to 1.48)	5.61×10⁽⁻⁶⁾	GENO	1.00 (0.79 to 1.25)	0.98	1.24 (1.12 to 1.38)	5.68×10⁽⁻⁵⁾
7	PRPS1L1	rs12699949	18010787	GENO	0.77 (0.69 to 0.87)	1.19×10⁽⁻⁵⁾	GENO	0.89 (0.72 to 1.10)	0.27	0.80 (0.72 to 0.88)	1.19×10⁽⁻⁵⁾
13	Intergenic	rs2496764	84477159	GENO	1.34 (1.18 to 1.52)	7.86×10⁽⁻⁶⁾	GENO	0.99 (0.78 to 1.27)	0.96	1.26 (1.12 to 1.41)	8.03×10⁽⁻⁵⁾
17	ERBB2	rs1810132	35119531	GENO	1.28 (1.14 to 1.43)	1.73×10⁽⁻⁵⁾	GENO	1.07 (0.86 to 1.32)	0.56	1.23 (1.11 to 1.36)	4.54×10⁽⁻⁵⁾
Four imputed SNPs in regions above with a lower p value than the original genotyped SNP in imputed SNP analyses
2	IL18R1	rs9807989	102337632	0.91	0.76 (0.67 to 0.85)	5.20×10⁽⁻⁶⁾	0.91	0.72 (0.58 to 0.89)	0.003	0.75 (0.68 to 0.83)	5.59×10⁽⁻⁸⁾
7	PRPS1L1	rs12699948	18010735	0.92	0.75 (0.66 to 0.85)	4.84×10⁽⁻⁶⁾	0.93	0.92 (0.74 to 1.15)	0.46	0.79 (0.71 to 0.88)	1.44×10⁽⁻⁵⁾
13	Intergenic	rs9547037	84476839	0.90	1.38 (1.20 to 1.58)	6.60×10⁽⁻⁶⁾	0.90	1.00 (0.78 to 1.29)	0.97	1.28 (1.13 to 1.44)	8.01×10⁽⁻⁵⁾
17	STARD3	rs9972882	35061224	0.98	1.32 (1.17 to 1.49)	5.17×10⁽⁻⁶⁾	0.99	1.07 (0.85 to 1.34)	0.55	1.26 (1.13 to 1.40)	1.64×10⁽⁻⁵⁾
Two SNPs with p>10⁽⁻⁵⁾ responsible for secondary peaks in regions with known asthma genes
2	IL1R1	rs13035227	102130269	0.96	1.36 (1.16 to 1.58)	8.91×10⁽⁻⁵⁾	GENO	1.53 (1.17 to 1.99)	0.002	1.40 (1.22 to 1.59)	6.69×10⁽⁻⁷⁾
5	IL13	rs847	132024568	0.86	1.35 (1.17 to 1.55)	4.05×10⁽⁻⁵⁾	0.94	1.12 (0.88 to 1.43)	0.37	1.29 (1.14 to 1.45)	6.43×10⁽⁻⁵⁾
Twelve SNPs from new regions identified by imputation with p<10⁽⁻⁵⁾ and r²_imp=0.7 (includes two secondary peaks in previously identified 17q12-21 region)
2	Intergenic	chr2:211694960	211694960	0.70	1.76 (1.40 to 2.21)	1.27×10⁽⁻⁶⁾	0.78	1.11 (0.73 to 1.70)	0.62	1.59 (1.30 to 1.94)	6.80×10⁽⁻⁶⁾
5	FLJ37543	rs7715669	60972053	GENO	0.74 (0.65 to 0.84)	5.92×10⁽⁻⁶⁾	GENO	0.93 (0.74 to 1.18)	0.56	0.78 (0.69 to 0.87)	2.29×10⁽⁻⁵⁾
5	NDFIP1	rs6867913	141426164	0.99	0.72 (0.63 to 0.82)	1.74×10⁽⁻⁶⁾	0.97	0.90 (0.69 to 1.15)	0.39	0.75 (0.67 to 0.85)	3.82×10⁽⁻⁶⁾
6	GCLC	rs9395865	53415653	GENO	0.76 (0.67 to 0.85)	5.27×10⁽⁻⁶⁾	GENO	1.15 (0.93 to 1.42)	0.19	0.84 (0.76 to 0.93)	9.27×10⁽⁻⁴⁾
6	Intergenic	rs6922932	73384242	0.78	0.70 (0.60 to 0.82)	7.36×10⁽⁻⁶⁾	0.83	1.02 (0.79 to 1.31)	0.88	0.78 (0.68 to 0.89)	1.99×10⁽⁻⁴⁾
8	DUSP4	rs650230	29322727	0.78	1.37 (1.19 to 1.57)	6.40×10⁽⁻⁶⁾	0.76	1.04 (0.83 to 1.30)	0.73	1.27 (1.13 to 1.42)	5.74×10⁽⁻⁵⁾
9	ACO1	rs10970976	32423526	0.98	0.76 (0.67 to 0.86)	9.14×10⁽⁻⁶⁾	0.96	0.84 (0.67 to 1.05)	0.13	0.78 (0.70 to 0.86)	3.69×10⁽⁻⁶⁾
11	OR52E4	rs4453217	5883859	0.87	1.43 (1.25 to 1.64)	2.82×10⁽⁻⁷⁾	0.88	0.94 (0.72 to 1.22)	0.63	1.31 (1.16 to 1.48)	1.50×10⁽⁻⁵⁾
11	ETS1	rs7125574	127866404	0.93	1.34 (1.18 to 1.51)	5.28×10⁽⁻⁶⁾	0.93	0.92 (0.73 to 1.16)	0.49	1.23 (1.10 to 1.37)	2.13×10⁽⁻⁴⁾
17	STAC2	rs9897185	34642935	GENO	1.31 (1.16 to 1.47)	1.19×10⁽⁻⁵⁾	GENO	0.95 (0.75 to 1.19)	0.64	1.22 (1.10 to 1.35)	2.50×10⁽⁻⁴⁾
17	ORMDL3	rs4794820	35342870	0.94	0.76 (0.68 to 0.85)	1.52×10⁽⁻⁶⁾	0.93	0.72 (0.59 to 0.89)	0.002	0.75 (0.69 to 0.83)	1.03×10⁽⁻⁸⁾
19	ZNF665	rs16984547	58373854	GENO	1.53 (1.30 to 1.82)	5.45×10⁽⁻⁷⁾	GENO	1.06 (0.76 to 1.49)	0.74	1.43 (1.23 to 1.66)	3.54×10⁽⁻⁶⁾

Effect allele refers to the minor allele. GENO denotes genotyped SNP. Significant p values p≤0.05 in replication, p<5×10⁽⁻⁸⁾ in meta-analysis are shown in bold. The gene tagged by the SNP due to linkage disequilibrium (LD) block structure within the locus is listed.
AAGC, Australian Asthma Genetics Consortium; AUGOSA, Asthma UK Genetics of Severe Asthma.