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HLA ‐ DQ strikes again: Genome‐wide association study further confirms HLA ‐ DQ in the diagnosis of asthma among adults
Author(s) -
LaskySu J.,
Himes B. E.,
Raby B. A.,
Klanderman B. J.,
Sylvia J. Senter,
Lange C.,
Melen E.,
Martinez F. D.,
Israel E.,
Gauderman J.,
Gilliland F.,
Sleiman P.,
Hakonarson H.,
Celedón J. C.,
SotoQuiros M.,
Avila L.,
Lima J. J.,
Irvin C. G.,
Peters S. P.,
Boushey H.,
Chinchilli V. M.,
Mauger D.,
Tantisira K.,
Weiss S. T.
Publication year - 2012
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12000
Subject(s) - asthma , genome wide association study , human leukocyte antigen , single nucleotide polymorphism , snp , immunology , genetic association , hla dq , genetics , medicine , biology , gene , genotype , antigen , haplotype
Summary Background Asthma is a common chronic respiratory disease in children and adults. An important genetic component to asthma susceptibility has long been recognized, most recently through the identification of several genes (e.g., ORMDL 3, PDE 4D, HLA ‐ DQ , and TLE 4) via genome‐wide association studies. Objective To identify genetic variants associated with asthma affection status using genome‐wide association data. Methods We describe results from a genome‐wide association study on asthma performed in 3855 subjects using a panel of 455 089 single nucleotide polymorphisms ( SNP s). Result The genome‐wide association study resulted in the prioritization of 33 variants for immediate follow‐up in a multi‐staged replication effort. Of these, a common polymorphism (rs9272346) localizing to within 1 Kb of HLA ‐ DQA 1 (chromosome 6p21.3) was associated with asthma in adults ( P ‐value = 2.2E‐08) with consistent evidence in the more heterogeneous group of adults and children ( P ‐value = 1.0E‐04). Moreover, some genes identified in prior asthma GWAS were nominally associated with asthma in our populations. Conclusion Overall, our findings further replicate the HLA ‐ DQ region in the pathogenesis of asthma. HLA ‐ DQA 1 is the fourth member of the HLA family found to be associated with asthma, in addition to the previously identified HLA ‐ DRA , HLA ‐ DQB 1 and HLA ‐ DQA 2.