Overview

The first large-scale genome-wide association study (GWAS) of allergic sensitization was performed in 5,789 affected individuals and 10,056 controls and the top SNP at each of 26 loci in 6,114 affected individuals and 9,920 controls were followed up. The number of susceptibility loci with genome-wide significant association were increased with allergic sensitization from three to ten, including SNPs in or near TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B. All the top SNPs were associated with allergic symptoms in an independent study. Risk-associated variants at these ten loci were estimated to account for at least 25% of allergic sensitization and allergic rhinitis. Meta-analysis of association data for ~2.5 million imputed and genotyped autosomal SNPs was performed using additive model fixed-effects meta-analysis as implemented in METAL.

Study Type
Whole Genome Association Study
Samples
GroupPhenotypePopulationCasesControlsFamiliesTrios
DiscoveryIGECEU578910056--
ReplicationIGECEU61149920--
Exclusion Criteria

Discovery: SNPs were excluded based on:

  • minor allele frequency (MAF) of <1%

  • poor imputation quality (r2 < 0.3, if using the imputation algorithm MaCH, or proper info <0.4, if using the IMPUTE imputation algorithm)

Replication: SNPs were excluded if they were not the most strongly associated in one of the 26 most strongly associated loci (P < 10-5 in stage 1).

Study Association

RegionLocationGene(s)MarkerAlleleMAFP ValueOdds Ratio
1q24.3chr1:172682989-172960924FASLG  rs859624C > T0.2402.70e-05C1.14 (1.08-1.21)D
2q12.1chr2:102238422-102637484IL18RAP  SLC9A4  rs6759479A > C0.5004.80e-05C1.12 (1.06-1.18)D
2q12.1chr2:102193725-102584846IL18R1  IL1RL1  rs3771175T > A0.1404.90e-11C1.27 (1.14-1.39)D
2q13chr2:111666171-111886554ANAPC1  rs11122895C > T0.3901.50e-06C1.14 (1.08-1.20)D
3p24.3chr3:20910460-21070084rs6807490A > C0.1502.30e-03C1.19 (1.10-1.28)D
3q28chr3:188351572-188421362LPP  rs9865818A > G0.4102.70e-10C1.14 (1.08-1.19)D
4p14chr4:38740298-38905457TLR6  TLR10  TLR1  rs17616434T > C0.2205.20e-11C1.23 (1.16-1.32)D
4p16.1chr4:11128121-11283615rs12511580G > A0.3305.10e-04C1.14 (1.07-1.21)D
4q27chr4:122041392-122644147ADAD1  IL2  rs17454584A > G0.2605.50e-10C1.14 (1.08-1.20)D
5q22.1chr5:110366888-111065770SLC25A46  rs10056340T > G0.1705.20e-14C1.22 (1.14-1.30)D
5q33.3chr5:160433243-160546594SLU7  rs2961919A > G0.3202.30e-03C1.14 (1.08-1.2)D
5q35.1chr5:170076072-170203298rs1469066T > C0.3803.60e-04C1.12 (1.08-1.19)D
6p12.1chr6:56291327-56626042COL21A1  rs16887812C > T0.3506.70e-06C1.13 (1.07-1.20)D
6p24.3chr6:9820949-10037773OFCC1  rs12201441G > A0.3402.90e-02C1.15 (1.09-1.22)D
6q14.1chr6:80842376-81224888rs9344121T > G0.2409.30e-05C1.15 (1.08-1.22)D
6q15chr6:87104484-87777966AKIRIN2  ORC3  rs9294385C > A0.2703.30e-05C1.15 (1.08-1.22)D
8q24.21chr8:127741008-127890277PVT1  MYC  rs4410871C > T0.2805.40e-10C1.16 (1.09-1.23)D
11q13.5chr11:76324636-76632292EMSY  rs2155219G > T0.4701.40e-18C1.20 (1.14-1.24)D
12p13.31chr12:6179942-6263242CD9  rs3181295G > A0.4203.10e-04C1.12 (1.07-1.18)D
12q13.3chr12:56904296-57164722STAT6  rs1059513T > C0.1001.00e-14C1.33 (1.22-1.47)D
15q14chr15:38672374-38722713C15orf53  rs12912542A > C0.2901.20e-03C1.14 (1.08-1.20)D
16p12.1chr16:25910900-25977505HS3ST4  rs9937695A > G0.4009.30e-05C1.12 (1.08-1.19)D
18q12.2chr18:38930976-39563615rs7350983T > C0.1003.60e-04C1.22 (1.12-1.33)D
22q13.32chr22:48619256-48683202FAM19A5  rs5771884C > T0.2005.20e-04C1.16 (1.1-1.25)D
MHCchr6:32428165-32715547HLA-DQB1  rs6906021T > C0.4502.20e-12C1.16 (1.10-1.22)D
MHCchr6:31338643-31469528MICA  HLA-B  rs6932730T > C0.1804.20e-08C1.18 (1.1-1.27)D

Criteria

GDXHsS00049 meets the following criteria:

Criteria Name
Details
Disease Tags
Study for a Disease 

Publications

PMIDTitleFirst AuthorJournalDisease(s)Date