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, Aida Eslami, C. Dorien van Ginkel, Loubna Akhabir, Ming Wan, George Ellis, Moshe Ben-Shoshan, David Martino, Manuel A. Ferreira, Katrina Allen, Bruce Mazer, Hans de Groot, Nicolette W. de Jong, Roy N. Gerth van Wijk, Anthony E.J. Dubois, Rick Chin, Stephen Cheuk, Joshua Hoffman, Eric Jorgensen, John S. Witte & 11 others Ronald B. Melles, Xiumei Hong, Xiaobin Wang, Jennie Hui, Arthur W. Musk, Michael Hunter, Alan L. James, Gerard H. Koppelman, Andrew J. Sandford, Ann E. Clarke, Denise Daley

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)991-1001
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number3
DOIs
Publication statusPublished - Mar 2018

Fingerprint

Peanut Hypersensitivity
Food Hypersensitivity
Genome-Wide Association Study
Meta-Analysis
Single Nucleotide Polymorphism
Population
src-Family Kinases
Phosphoproteins
Metalloproteases
Genome
Phenotype
Catenins
Chromosomes, Human, Pair 11
Gene Expression Regulation
Genetic Predisposition to Disease
Epigenomics
Integrins
Open Reading Frames
Genes

Cite this

Asai, Yuka ; Eslami, Aida ; van Ginkel, C. Dorien ; Akhabir, Loubna ; Wan, Ming ; Ellis, George ; Ben-Shoshan, Moshe ; Martino, David ; Ferreira, Manuel A. ; Allen, Katrina ; Mazer, Bruce ; de Groot, Hans ; de Jong, Nicolette W. ; Gerth van Wijk, Roy N. ; Dubois, Anthony E.J. ; Chin, Rick ; Cheuk, Stephen ; Hoffman, Joshua ; Jorgensen, Eric ; Witte, John S. ; Melles, Ronald B. ; Hong, Xiumei ; Wang, Xiaobin ; Hui, Jennie ; Musk, Arthur W. ; Hunter, Michael ; James, Alan L. ; Koppelman, Gerard H. ; Sandford, Andrew J. ; Clarke, Ann E. ; Daley, Denise. / 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. In: Journal of Allergy and Clinical Immunology. 2018 ; Vol. 141, No. 3. pp. 991-1001.
@article{317828f4e1bd41f489913155f69d22be,
title = "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",
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, Epigenetics, Food allergy, Genome-wide association study, Meta-analysis, Peanut allergy",
author = "Yuka Asai and Aida Eslami and {van Ginkel}, {C. Dorien} and Loubna Akhabir and Ming Wan and George Ellis and Moshe Ben-Shoshan and David Martino and Ferreira, {Manuel A.} and Katrina Allen and Bruce Mazer and {de Groot}, Hans and {de Jong}, {Nicolette W.} and {Gerth van Wijk}, {Roy N.} and Dubois, {Anthony E.J.} and Rick Chin and Stephen Cheuk and Joshua Hoffman and Eric Jorgensen and Witte, {John S.} and Melles, {Ronald B.} and Xiumei Hong and Xiaobin Wang and Jennie Hui and Musk, {Arthur W.} and Michael Hunter and James, {Alan L.} and Koppelman, {Gerard H.} and Sandford, {Andrew J.} and Clarke, {Ann E.} and Denise Daley",
year = "2018",
month = "3",
doi = "10.1016/j.jaci.2017.09.015",
language = "English",
volume = "141",
pages = "991--1001",
journal = "The Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Elsevier - Mosby",
number = "3",

}

Asai, Y, Eslami, A, van Ginkel, CD, Akhabir, L, Wan, M, Ellis, G, Ben-Shoshan, M, Martino, D, Ferreira, MA, Allen, K, Mazer, B, de Groot, H, de Jong, NW, Gerth van Wijk, RN, Dubois, AEJ, Chin, R, Cheuk, S, Hoffman, J, Jorgensen, E, Witte, JS, Melles, RB, Hong, X, Wang, X, Hui, J, Musk, AW, Hunter, M, James, AL, Koppelman, GH, Sandford, AJ, Clarke, AE & Daley, D 2018, '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' Journal of Allergy and Clinical Immunology, vol. 141, no. 3, pp. 991-1001. https://doi.org/10.1016/j.jaci.2017.09.015

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. / Asai, Yuka; Eslami, Aida; van Ginkel, C. Dorien; Akhabir, Loubna; Wan, Ming; Ellis, George; Ben-Shoshan, Moshe; Martino, David; Ferreira, Manuel A.; Allen, Katrina; Mazer, Bruce; de Groot, Hans; de Jong, Nicolette W.; Gerth van Wijk, Roy N.; Dubois, Anthony E.J.; Chin, Rick; Cheuk, Stephen; Hoffman, Joshua; Jorgensen, Eric; Witte, John S.; Melles, Ronald B.; Hong, Xiumei; Wang, Xiaobin; Hui, Jennie; Musk, Arthur W.; Hunter, Michael; James, Alan L.; Koppelman, Gerard H.; Sandford, Andrew J.; Clarke, Ann E.; Daley, Denise.

In: Journal of Allergy and Clinical Immunology, Vol. 141, No. 3, 03.2018, p. 991-1001.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Asai, Yuka

AU - Eslami, Aida

AU - van Ginkel, C. Dorien

AU - Akhabir, Loubna

AU - Wan, Ming

AU - Ellis, George

AU - Ben-Shoshan, Moshe

AU - Martino, David

AU - Ferreira, Manuel A.

AU - Allen, Katrina

AU - Mazer, Bruce

AU - de Groot, Hans

AU - de Jong, Nicolette W.

AU - Gerth van Wijk, Roy N.

AU - Dubois, Anthony E.J.

AU - Chin, Rick

AU - Cheuk, Stephen

AU - Hoffman, Joshua

AU - Jorgensen, Eric

AU - Witte, John S.

AU - Melles, Ronald B.

AU - Hong, Xiumei

AU - Wang, Xiaobin

AU - Hui, Jennie

AU - Musk, Arthur W.

AU - Hunter, Michael

AU - James, Alan L.

AU - Koppelman, Gerard H.

AU - Sandford, Andrew J.

AU - Clarke, Ann E.

AU - Daley, Denise

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - C11orf30

KW - EMSY

KW - Epigenetics

KW - Food allergy

KW - Genome-wide association study

KW - Meta-analysis

KW - Peanut allergy

UR - http://www.scopus.com/inward/record.url?scp=85033374056&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2017.09.015

DO - 10.1016/j.jaci.2017.09.015

M3 - Article

VL - 141

SP - 991

EP - 1001

JO - The Journal of Allergy and Clinical Immunology

JF - The Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -