title: Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.
abstract: BACKGROUND
  To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever.
  
  
  OBJECTIVE
  We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases.
  
  
  METHODS
  We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091).
  
  
  RESULTS
  At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10(-9)) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10(-8)). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10(-7)) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10(-6)).
  
  
  CONCLUSIONS
  By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency.
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia. Electronic address: manuel.ferreira@qimrberghofer.edu.au.
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authors.lastname: Ferreira
authors.affiliation: Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
authors.forename: Melanie C
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authors.lastname: Matheson
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia; Departments of Psychiatry, Surgery, and Medicine, Centre for Genomic Sciences, University of Hong Kong, Hong Kong, China.
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authors.lastname: Tang
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Raquel
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authors.lastname: Granell
authors.affiliation: School of Women's and Infant's Health, University of Western Australia, Subiaco, Australia.
authors.forename: Wei
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authors.affiliation: PathWest Laboratory Medicine of Western Australia, Nedlands, Australia; School of Population Health, University of Western Australia, Nedlands, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia; Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia.
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authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: David L
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authors.lastname: Duffy
authors.affiliation: Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia.
authors.forename: Svetlana
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authors.lastname: Baltic
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
authors.forename: Patrick
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authors.lastname: Danoy
authors.affiliation: Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
authors.forename: Minh
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authors.lastname: Bui
authors.affiliation: Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia.
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authors.affiliation: Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, Australia.
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authors.affiliation: Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia.
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authors.affiliation: Telethon Institute of Child Health Research, University of Western Australia, Subiaco, Australia.
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authors.initials: PG
authors.lastname: Holt
authors.affiliation: Department of Psychiatry, Washington University School, of Medicine, St Louis, Mo.
authors.forename: Andrew C
authors.initials: AC
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authors.affiliation: School of Population Health, University of Western Australia, Nedlands, Australia; Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia.
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authors.lastname: Hunter
authors.affiliation: School of Population Health, University of Western Australia, Nedlands, Australia; Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
authors.forename: Bill
authors.initials: B
authors.lastname: Musk
authors.affiliation: Respiratory Medicine, Murdoch Children's Research Institute, Melbourne, Australia.
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authors.initials: CF
authors.lastname: Robertson
authors.affiliation: School of Paediatrics and Child Health, Princess Margaret Hospital for Children, Perth, Australia.
authors.forename: Peter
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authors.lastname: Le Souëf
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
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authors.initials: GW
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authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
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authors.lastname: Tung
authors.affiliation: Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
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authors.initials: SC
authors.lastname: Dharmage
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.affiliation: Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia; Department of Pulmonary Physiology, West Australian Sleep Disorders Research Institute, Nedlands, Australia.
authors.forename: Alan
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authors.affiliation: Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia.
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authors.affiliation: School of Women's and Infant's Health, University of Western Australia, Subiaco, Australia.
authors.forename: Craig
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authors.lastname: Pennell
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom.
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
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authors.initials: DA
authors.lastname: Hinds
authors.affiliation: Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia. Electronic address: j.hopper@unimelb.edu.au.
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authors.initials: JL
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mesh_terms: D000328:Adult; D000483:Alleles; D001249:Asthma / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012097:Repressor Proteins / Q000235:genetics; D006255:Rhinitis, Allergic, Seasonal / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
chemical_list: C522505:CLEC16A protein, human; D037181:Lectins, C-Type; D009004:Monosaccharide Transport Proteins; D012097:Repressor Proteins; C559929:ZBTB10 protein, human
keywords: Rhinitis; atopy; bivariate; genetic correlation; selection; single nucleotide polymorphism