Genome-wide association studies in asthma: progress and pitfalls

Figures & data

Table 1 Summary of asthma meta-analysis loci referenced in this review, including chromosome location, the most significant SNP identified, and the end point of the study

Reported gene	Locus	Top SNP	End point analyzed	Study
Asthma meta-analyses
ILIRLI/ILI8RI	2q12.1	rs3771166	Asthma in North American	Moffatt et al^l0
HLA-DQ	6p21.32	rs9273349	populations: meta-analysis
IL33	9p24.1	rs1342326	from the GABRIEL consortium
SMAD3	15q22.33	rs744910
IL2RB	22q12.3	rs2284033
ORMDL3/GSDMB	17q12	rs2305480
GSDMB	17q12	rs11078927	Asthma in four ethnically	Torgerson et al^Citation11
ILIRLI	2q12.1	rs10173081	diverse North American
TSLP	5q22.1	rs1837253	populations: meta-analysis
IL33	9p24.1	rs2381416	from the EVE consortium
PYHINI	1q23.1	rs1102000
CIIorf71	11q23.2	rs11214966
CRCTI	1q21.3	rs4845783

Abbreviation: SNP, single-nucleotide polymorphism.

Table 2 Summary of asthma-susceptibility GWA-study loci referenced in this review, including chromosome location, the most significant SNP identified, and the end point of the study

Reported gene	Locus	Top SNP	End point analyzed	Study
Asthma-susceptibility loci
ORMDL3	17q12	rs7216389	Childhood-onset asthma	Moffatt et al^Citation15
TLE4	9q21.31	rs2378383	Childhood-onset asthma	Hancock et al^Citation21
PDE4D	5q12.1	rs1588265	Childhood-onset asthma	Himes et al^Citation20
RAD50	5q31.1	rs2244012	Severe or difficult-to-control asthma	Li et al^Citation12
HLA-DR/DQ	6p21.32	rs3998159
HLA-DPA1/HLA-DPB1	6p21.3	rs987870	Childhood-onset asthma	Noguchi et al^Citation22
DENNDIB	1q31.3	rs2786098	Childhood-onset asthma	Sleiman et al^Citation16
IL6R	1q21.3	rs4129267	Asthma	Ferreira et al^Citation28
C11orf30/LRRC32	11q13.5	rs7130588
USP38-GABI	4q31	rs7686660	Asthma	Hirota et al^Citation29
TSLP/WDR36	5q22	rs1837253
NOTCH4/HLA-DRA/HLA-DQA2/IKZF4	6p21.32	rs404860
LOC338591	10p14	rs10508372
IKZF4/CDK2	12q13	rs1701704
ORMDL3	17q12	rs6503525	Asthma	Ferreira et al^Citation18
C1orf10	1q44	rs4658627	Childhood-onset asthma	Forno et al^Citation24
IL5RA	3p26.2	rs9815663
IL1RL1, IL18R1	2q12.1	rs13408661	Asthma	Ramasamy et al^Citation30
BTNL2, HLA-DRA	6p21.32	rs9268516
HLA-DQA1	6p21.32	rs9272346	Asthma	Lasky-Su et al^Citation27
ORMDL3	17q12	rs4794820	Severe asthma	Wan et al^Citation19
IL18R1, IL1R1	2q12.1	rs9807989
C5orf56	5q31.1	rs11745587
ACO1	9p21.1	rs10970976
ZNF665	19q13.42	rs16984547
NDFIP1	5q31.3	rs6867913
IGSF3	1p13.1	rs17036023	Childhood-onset	Ding et al^Citation25
HPSE2	10q24.2	rs12570188	Severe asthma
PSAP	10q22.1	rs11000019
ATG3	3q13.2	rs2705520
MKLN1	7q32.3	rs7807274
XPR1	1q25.3	rs7527074
ABI3BP	3q12.2	rs9823506
KLHL5	4p14	rs35141484
CDHR3	7q22.3	rs6967330	Childhood-onset asthma with exacerbations	Bonnelykke et al^Citation26
HLA-DQB1	6p21.32	rs9273373	Asthma and hay fever	Ferreira et al^Citation17
TLR1	4p14	rs4833095
WDR36	5q22.1	rs1438673
IL1RL1	2q12.1	rs10197862
GSDMA	17q21.1	rs7212938
TSLP	5q22.1	rs1837253
IL33	9p24.1	rs72699186
SMAD3	15q22.33	rs17294280
ZBTB10	8q21.13	rs7009110
CLEC16A	16p13.13	rs62026376

Abbreviations: GWA, genome-wide association; SNP, single-nucleotide polymorphism.

Table 3 Summary of lung-function GWA-study loci referenced in this review, including chromosome location, the most significant SNP identified, and the end point of the study

Reported gene	Locus	Top SNP	End point analyzed	Study
Lung-function genes
CHRNA3/5	15q24	rs8034191	COPD	Pillai et al^Citation31
HHIP	4q3l.22	rs13147758	FEV/FVC	Wilk et al^Citation34
FAM13A	4q22.l	rs7671167	COPD	Cho et al^Citation69
HHIP	4q31.22	rs1980057	FEVI/FVC	Hancock et al^Citation32
GPRI26	6q24.l	rs3817928	FEV/FVC
ADAM19	5q33	rs2277027	FEV/FVC
AGER-PPT2	6p21.3	rs2070600	FEV/FVC
FAMI3A	4q22.l	rs2869967	FEV/FVC
PTCHI	9q22.32	rs16909898	FEV/FVC
PIDI	2q36.3	rs1435867	FEV/FVC
HTR4	5q33.l	rs11168048	FEV/FVC
INTSI2-GSTCD-NPNT	4q24	rs17331332	FEVI
TNSI	2q35	rs2571445	FEVI	Repapi et al^Citation33
GSTCD	4q24	rs10516526	FEVI
HHIP	4q31.22	rs12504628	FEV/FVC
HTR4	5q33.l	rs3995090	FEVI
AGER	6p21.32	rs2070600	FEVI/FVC
THSD4	15q23	rs12899618	FEV/FVC
MFAP2	1p36.13	rs2284746	FEV/FVC	Soler Artigas et al^Citation36
TGFB2	1q41	rs993925	FEV/FVC
HDAC4	2q37.3	rs12477314	FEV/FVC
RARB	3p24	rs1529672	FEV/FVC
MECOM	3q26	rs1344555	FEVI
SPATA9	5q15	rs153916	FEV/FVC
ZKSCAN3	6p22.1	rs6903828	FEVI
NCR3	6p21.3	rs2857595	FEVI/FVC
ARMC2	6q21	rs2798641	FEV/FVC
C10orf11	10q22.2	rs11001819	FEVI
LRP1	12q13.3	rs11172113	FEV/FVC
CCDC38	12q23.1	rs1036429	FEV/FVC
MMP15	16q21	rs12447804	FEV/FVC
CFDP1	16q23.1	rs2865531	FEV/FVC
KCNE2	21q22.1	rs9978142	FEV/FVC
DNER	2q36.3	rs7594321	Smoking-associated declines in FEV/FVC	Hancock et al^Citation38
HLA-DQB1, HLA-DQA2	6p21.32	rs7764819
KCNJ2, SOX9	17q24.3	rs11654749
UPK3A	22q13.31	rs58667	FEV/FVC	Li et al^Citation35
EMX2	10q26.11	rs4752066	FEV/FVC
YES1	18p11.32	rs1291183	FEV/FVC
IL12RB1	19p13.11	rs12984174	FEV/FVC
THSD4, TLE3, UACA	15q23	rs12441227	FEVI	Yao et al^Citation37
CDH2	18q12.1	rs879500	FVC (caucasians)	Ong et al^Citation39
MYBPCI	12q23.2	rs10860757	FVC (caucasians)
CTNNA3	10q21.3	rs1471384	FVC (African Americans)
INTS12/GSTCD	4q24	rs1982346	FEVI (meta-analysis)

Abbreviations: GWA, genome-wide association; SNP, single-nucleotide polymorphism; COPD chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Table 4 Summary of asthma biomarker-associated GWA-study loci referenced in this review, including chromosome location, the most significant SNP identified, and the end point of the study

Reported gene	Locus	Top SNP	End point analyzed	Study
Biomarker associations
FCER1A	1q23.2	rs2427837	Serum IgE levels	weidinger et al^Citation46
STAT6	12q13	rs12368672
RAD50	5q31.1	rs2706347
CHI3L1	1q32.1	rs4950928	Asthma/YKL-40 serum levels	Ober et al^Citation45
IL1RL1	2q12.1	rs1420101	Asthma/blood eosinophil count	Gudbjartsson et al^Citation50
IKZF2	5q31.1	rs12619285
GATA2	3q21.3	rs4857855
IL5	2q12.1	rs4143832
SH2B3	12q24.12	rs3184504
C11orf30/LRRC32	11q13.5	rs2155219	Allergic rhinitis/grass	Ramasamy et al^Citation70
TMEM232/SLCA25A46	5q22.1	rs17513503	sensitization
HLA region	6p21	rs7775228
FCER1A	1q23.2	rs2251746	IgE levels	Granada et al^Citation71
ILI3	5q31.1	rs20541
HLA-A	6p22.1	rs2571391
STAT6/NAB2	12q13.3	rs1059513
DARC	1q23.2	rs13962
HLA-DQA2	6p21.32	rs2858331
PTBP2	1p21.3	rs321588	Serum total	Levin et al^Citation47
SUCLG2	3p14.1	rs2363709	IgE levels
MAT2B	5q34	rs13361473
HLA-DQB1	6p21.32	rs9469220
TBX18	6q14.2	rs10944017
SOBP	6q21	rs7751374
TLE4	9q21.31	rs10124954
CCDC82	11q21	rs537526
WWP2	16q22.1	rs6499255
LINC00469	17q25.1	rs16977747
LYRM9	17q12	rs3751972	FeNO	van der Valk et al^Citation72
NOS2	17q12	rs944722
GSDMB	17q12	rs8069176
TLR1/TLR6	4p14	rs2101521	Cat, dust-mite, and pollen allergies	Hinds et al^Citation49
WDR36/CAMK4	5q22.1	rs1438673
C11orf30/LRRC32	11q13.5	rs2155219
IL1RL2/IL1RL1	2q12.1	rs10189629
HLA-DQA1/HLA-DQB1	6p21.32	rs6906021
HLA-C/MICA	6p21.33	rs9266772
PTGER4	5p13.1	rs7720838
PLCL1	2q33.1	rs10497813
LPP	3q28	rs9860547
RANBP6/IL33	9p24.1	rs7032572
NFATC2	20q13.2	rs6021270
GSDMB	17q12	rs9303280
SMAD3	15q22.33	rs17228058
GATA3	10p14	rs962993
ADAD1	4q27	rs17388568
FOXA1/TTC6	14q21.1	rs1998359
TPD52/ZBTB10	8q21.13	rs6473223
ID2	2p25.1	rs10174949
CLEC16A	16p13.13	rs7203459
IL4R/IL21R	16p12.1	rs2107357
PEX14	1p36.22	rs2056417
ETS1	11q24.3	rs10893845

Abbreviations: GWA, genome-wide association; SNP, single-nucleotide polymorphism.

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