@article{7f534c89eaec4279b68661bc4d5aaa49,
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). 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.",
keywords = "Rhinitis, atopy, bivariate, genetic correlation, selection, single nucleotide polymorphism",
author = "Ferreira, {Manuel A.R.} and Matheson, {Melanie C.} and Tang, {Clara S.} and Raquel Granell and Wei Ang and Jennie Hui and Kiefer, {Amy K.} and Duffy, {David L.} and Svetlana Baltic and Patrick Danoy and Minh Bui and Loren Price and Sly, {Peter D.} and Nicholas Eriksson and Madden, {Pamela A.} and Abramson, {Michael J.} and Holt, {Patrick G.} and Heath, {Andrew C.} and Michael Hunter and Bill Musk and Robertson, {Colin F.} and {Le Sou{\"e}f}, Peter and Montgomery, {Grant W.} and Henderson, {A. John} and Tung, {Joyce Y.} and Dharmage, {Shyamali C.} and Brown, {Matthew A.} and Alan James and Thompson, {Philip J.} and Craig Pennell and Martin, {Nicholas G.} and Evans, {David M.} and Hinds, {David A.} and Hopper, {John L.}",
note = "Funding Information: Disclosure of potential conflict of interest: M. A. R. Ferreira has received research support from the Australian National Health and Medical Research Council (NHMRC) . A. K. Kiefer has received research support from the National Institutes of Health (NIH) and is employed by and has stock/stock options in 23andMe. D. L Duffy has received research support from the NHMRC. N. Eriksson has received research support from the NIH and is employed by and has stock/stock options in 23andMe. P. A. Madden has received research support from the NIH ( R01DA012854 [NAG] and R25DA027995 [R25]) and has received lecture fees. M. J. Abramson has received research support from Pfizer and has received travel support from Boehringer Ingelheim. A. C. Heath has received research support from the National Institutes of Health . C. F. Robertson has received research support from the NHMRC (grants 436959 , 490321 , 491246 , 1006215 , 044816 , and 1044829 ), the MCRI , the US Cystic Fibrosis Foundation , the Australian Cystic Fibrosis Research Trust , and the NHMRC Centre for Research Excellence . G. W. Montgomery has received research support from the NHMRC . A. J. Henderson has received research support from the Medical Research Council UK and the Wellcome Trust . J. Y. Tung has received research support from the NIH ( 1R43HL115873-01 ) and is employed by and has stock/stock options in 23andMe. C. Pennell has received research support from the NHMRC ( APP572613 , 2009-2012), the NIH , CIHR , and Channel 7 Telethon ; is a board member for the Raine Executive Committee; is employed by the University of Western Australia; has patents from the United States; and has received travel expenses from the March of Dimes Preventing Prematurity meeting, the GAPPS meeting, and PreHOT meetings from 2009-2012. D. M. Evans has received research support from the MRC and the Wellcome trust (supply core support to Avon Longitudinal Study of Parents and Their Children). D. A. Hinds has received research support from the NIH ( 1R43HL115873-01 ) and is employed by and has stock/stock options in 23andMe. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: Supported by the Australian National Health and Medical Research Council (NHMRC; grants 241944 , 339462 , 389927 , 389875 , 389891 , 389892 , 389938 , 442915 , 442981 , 496739 , 552485 , 552498 , 613627 , 403981 , and 003209 ); the Australian Research Council (grants A7960034 , A79906588 , A79801419 , DP0770096 , DP0212016 , and DP0343921 ); the FP-5 GenomEUtwin Project ( QLG2-CT-2002-01254 ); the US National Institutes of Health (grants AA07728 , AA07535 , AA10248 , AA11998 , AA13320 , AA13321 , AA13326 , AA14041 , AA17688 , DA12854 , and MH66206 ); Asthma Foundations in Tasmania, Queensland, and Victoria; the Clifford Craig Trust in Northern Tasmania; the Lew Carty Foundation; the Royal Hobart Research Foundation ; the University of Melbourne; the Great Wine Estates of the Margaret River region of Western Australia; the University of Western Australia (UWA); Raine Medical Research Foundation ; UWA Faculty of Medicine, Dentistry and Health Sciences ; the Telethon Institute for Child Health Research; the Women and Infants Research Foundation ; the Canadian Institutes of Health Research ( MOP-82893 ); and the National Heart, Lung, and Blood Institute of the National Institutes of Health under grant no. 1R43HL115873-01 . ",
year = "2014",
month = jun,
doi = "10.1016/j.jaci.2013.10.030",
language = "English",
volume = "133",
pages = "1564--1571",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
number = "6",
}