PuSH - Publikationsserver des Helmholtz Zentrums München

Margaritte-Jeannin, P.* ; Budu-Aggrey, A.* ; Ege, M. ; Madore, A.M.* ; Linhard, C.* ; Mohamdi, H.* ; von Mutius, E.* ; Granell, R.* ; Demenais, F.* ; Laprise, C.* ; Bouzigon, E.* ; Dizier, M.H.*

Identification of OCA2 as a novel locus for the co-morbidity of asthma-plus-eczema.

Clin. Exp. Allergy 52, 70-81 (2022)
DOI PMC
BACKGROUND: Numerous genes have been associated with the three most common allergic diseases (asthma, allergic rhinitis or eczema) but these genes explain only a part of the heritability. In the vast majority of genetic studies, complex phenotypes such as co-morbidity of two of these diseases, have not been considered. This may partly explain missing heritability. OBJECTIVE: To identify genetic variants specifically associated with the co-morbidity of asthma-plus-eczema. METHODS: We first conducted a meta-analysis of four GWAS (Genome-Wide Association Study) of the combined asthma-plus-eczema phenotype (total of 8807 European-ancestry subjects of whom 1208 subjects had both asthma and eczema). To assess whether the association with SNP(s) was specific to the co-morbidity, we also conducted a meta-analysis of homogeneity test of association according to disease status ("asthma-plus-eczema" vs. the presence of only one disease "asthma only or eczema only"). We then used a joint test by combining the two test statistics from the co-morbidity-SNP association and the phenotypic heterogeneity of SNP effect meta-analyses. RESULTS: Seven SNPs were detected for specific association to the asthma-plus-eczema co-morbidity, two with significant and five with suggestive evidence using the joint test after correction for multiple testing. The two significant SNPs are located in the OCA2 gene (Oculocutaneous Albinism II), a new locus never detected for significant evidence of association with any allergic disease. This gene is a promising candidate gene, because of its link to skin and lung diseases, and to epithelial barrier and immune mechanisms. CONCLUSION: Our study underlines the importance of studying sub-phenotypes as co-morbidities to detect new susceptibility genes.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Alspac ; Egea ; Gabriela ; Gwas ; Slsj ; Asthma ; Co-morbidity ; Eczema ; Phenotypic Heterogeneity
ISSN (print) / ISBN 0954-7894
e-ISSN 1365-2222
Zeitschrift Clinical & Experimental Allergy
Quellenangaben Band: 52, Heft: 1, Seiten: 70-81 Artikelnummer: , Supplement: ,
Verlag Wiley
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Asthma and Allergy Prevention (IAP)
Förderungen Wellcome Trust
Medical Research Council