title: HLA-DQ strikes again: genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults.
abstract: 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., ORMDL3, PDE4D, HLA-DQ, and TLE4) 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 (SNPs).
  
  
  RESULTS
  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-DQA1 (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.
  
  
  CONCLUSIONS
  Overall, our findings further replicate the HLA-DQ region in the pathogenesis of asthma. HLA-DQA1 is the fourth member of the HLA family found to be associated with asthma, in addition to the previously identified HLA-DRA, HLA-DQB1 and HLA-DQA2.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lasky-Su
authors.forename: B E
authors.initials: BE
authors.lastname: Himes
authors.forename: B A
authors.initials: BA
authors.lastname: Raby
authors.forename: B J
authors.initials: BJ
authors.lastname: Klanderman
authors.forename: J Senter
authors.initials: JS
authors.lastname: Sylvia
authors.forename: C
authors.initials: C
authors.lastname: Lange
authors.forename: E
authors.initials: E
authors.lastname: Melen
authors.forename: F D
authors.initials: FD
authors.lastname: Martinez
authors.forename: E
authors.initials: E
authors.lastname: Israel
authors.forename: J
authors.initials: J
authors.lastname: Gauderman
authors.forename: F
authors.initials: F
authors.lastname: Gilliland
authors.forename: P
authors.initials: P
authors.lastname: Sleiman
authors.forename: H
authors.initials: H
authors.lastname: Hakonarson
authors.forename: J C
authors.initials: JC
authors.lastname: Celedón
authors.forename: M
authors.initials: M
authors.lastname: Soto-Quiros
authors.forename: L
authors.initials: L
authors.lastname: Avila
authors.forename: J J
authors.initials: JJ
authors.lastname: Lima
authors.forename: C G
authors.initials: CG
authors.lastname: Irvin
authors.forename: S P
authors.initials: SP
authors.lastname: Peters
authors.forename: H
authors.initials: H
authors.lastname: Boushey
authors.forename: V M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: D
authors.initials: D
authors.lastname: Mauger
authors.forename: K
authors.initials: K
authors.lastname: Tantisira
authors.forename: S T
authors.initials: ST
authors.lastname: Weiss
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen