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J Allergy Clin Immunol. 2014 Jun;133(6):1564-71. doi: 10.1016/j.jaci.2013.10.030. Epub 2013 Dec 31.

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.

Author information

  • 1QIMR Berghofer Medical Research Institute, Brisbane, Australia. Electronic address: manuel.ferreira@qimrberghofer.edu.au.
  • 2Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
  • 3QIMR Berghofer Medical Research Institute, Brisbane, Australia; Departments of Psychiatry, Surgery, and Medicine, Centre for Genomic Sciences, University of Hong Kong, Hong Kong, China.
  • 4School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
  • 5School of Women's and Infant's Health, University of Western Australia, Subiaco, Australia.
  • 6PathWest 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.
  • 723andMe, Mountain View, Calif.
  • 8QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • 9Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia.
  • 10University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
  • 11Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, Australia.
  • 12Department of Psychiatry, Washington University School, of Medicine, St Louis, Mo.
  • 13Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia.
  • 14Telethon Institute of Child Health Research, University of Western Australia, Subiaco, Australia.
  • 15School of Population Health, University of Western Australia, Nedlands, Australia; Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia.
  • 16School 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.
  • 17Respiratory Medicine, Murdoch Children's Research Institute, Melbourne, Australia.
  • 18School of Paediatrics and Child Health, Princess Margaret Hospital for Children, Perth, Australia.
  • 19Busselton 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.
  • 20School 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.
  • 21Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia. Electronic address: j.hopper@unimelb.edu.au.

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)).

CONCLUSION:

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.

Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

KEYWORDS:

Rhinitis; atopy; bivariate; genetic correlation; selection; single nucleotide polymorphism

PMID:
24388013
[PubMed - indexed for MEDLINE]
PMCID:
PMC4280183
Free PMC Article

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