Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

Yuka Asai¹, Aida Eslami², C Dorien van Ginkel³, Loubna Akhabir², Ming Wan², George Ellis², Moshe Ben-Shoshan⁴, David Martino⁵, Manuel A Ferreira⁶, Katrina Allen⁵, Bruce Mazer⁴, Hans de Groot⁷, Nicolette W de Jong⁸, Roy N Gerth van Wijk⁸, Anthony E J Dubois³, Rick Chin⁹, Stephen Cheuk¹⁰, Joshua Hoffman¹¹, Eric Jorgensen¹², John S Witte¹¹, Ronald B Melles¹³, Xiumei Hong¹⁴, Xiaobin Wang¹⁴, Jennie Hui¹⁵, Arthur W Bill Musk¹⁶, Michael Hunter¹⁷, Alan L James¹⁸, Gerard H Koppelman³, Andrew J Sandford², Ann E Clarke¹², Denise Daley¹⁹

Affiliations

¹ Division of Dermatology, Department of Medicine, Queen's University, Kingston, and the Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.
² Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada.
³ University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology and University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
⁴ Division of Allergy and Immunology, Department of Pediatrics, Montreal Children's Hospital, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
⁵ Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Australia.
⁶ QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁷ Department of Pediatric Allergology, Diaconessenhuis Voorburg, Reinier de Graaf Gasthuis, Delft, The Netherlands.
⁸ Erasmus MC, Department of Allergology, Rotterdam, The Netherlands.
⁹ Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁰ Private Practice, Calgary, Alberta.
¹¹ Department of Epidemiology and Biostatistics, University of California, San Francisco, Calif.
¹² Division of Research, Kaiser Permanente Northern California, Oakland, Calif.
¹³ Department of Ophthalmology, Kaiser Permanente Northern California, Redwood City Medical Center, Redwood City, Calif.
¹⁴ Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Md.
¹⁵ School of Population Health, University of Western Australia, Australia and Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
¹⁶ Department of Respiratory Medicine, Sir Charles Gairdner Hospital, and School of Population Health, University of Western Australia, Perth, Australia.
¹⁷ School of Population Health, University of Western Australia, Perth, Australia.
¹⁸ Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
¹⁹ Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: denise.daley@hli.ubc.ca.

PMID: 29030101
DOI: 10.1016/j.jaci.2017.09.015

Free article

Meta-Analysis

Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

Yuka Asai et al. J Allergy Clin Immunol. 2018 Mar.

Free article

. 2018 Mar;141(3):991-1001.

doi: 10.1016/j.jaci.2017.09.015. Epub 2017 Oct 10.

Authors

Affiliations

¹ Division of Dermatology, Department of Medicine, Queen's University, Kingston, and the Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada.
² Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada.
³ University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology and University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
⁴ Division of Allergy and Immunology, Department of Pediatrics, Montreal Children's Hospital, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
⁵ Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Australia.
⁶ QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁷ Department of Pediatric Allergology, Diaconessenhuis Voorburg, Reinier de Graaf Gasthuis, Delft, The Netherlands.
⁸ Erasmus MC, Department of Allergology, Rotterdam, The Netherlands.
⁹ Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁰ Private Practice, Calgary, Alberta.
¹¹ Department of Epidemiology and Biostatistics, University of California, San Francisco, Calif.
¹² Division of Research, Kaiser Permanente Northern California, Oakland, Calif.
¹³ Department of Ophthalmology, Kaiser Permanente Northern California, Redwood City Medical Center, Redwood City, Calif.
¹⁴ Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Md.
¹⁵ School of Population Health, University of Western Australia, Australia and Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
¹⁶ Department of Respiratory Medicine, Sir Charles Gairdner Hospital, and School of Population Health, University of Western Australia, Perth, Australia.
¹⁷ School of Population Health, University of Western Australia, Perth, Australia.
¹⁸ Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
¹⁹ Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: denise.daley@hli.ubc.ca.

PMID: 29030101
DOI: 10.1016/j.jaci.2017.09.015

Abstract

Background: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis.

Objective: We sought to investigate genetic susceptibility to PA.

Methods: Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations.

Results: An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA (P = 1.80 × 10^-8), whereas SNPs associated with Src kinase-associated phosphoprotein 1 (SKAP1), matrix metallopeptidase 12 (MMP12)/MMP13, catenin α3 (CTNNA3), rho GTPase-activating protein 24 (ARHGAP24), angiopoietin 4 (ANGPT4), chromosome 11 open reading frame (C11orf30/EMSY), and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association (P ≤ 1.49 × 10^-6). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, C11orf30, and EXOC4 were significant (P ≤ 1.49 × 10^-6). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance (P = 7.50 × 10^-11), whereas SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, and EXOC4 and additional C11orf30 SNPs were suggestive (P ≤ 1.49 × 10^-6). Functional annotation indicated that SKAP1 regulates expression of CBX1, which colocalizes with the EMSY protein coded by C11orf30.

Conclusion: This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.

Keywords: C11orf30; EMSY; Peanut allergy; epigenetics; food allergy; genome-wide association study; meta-analysis.

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Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

Affiliations

Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials

Miscellaneous