möglich sobald bei der ZB eingereicht worden ist.
Identification of OCA2 as a novel locus for the co-morbidity of asthma-plus-eczema.
Clin. Exp. Allergy 52, 70-81 (2022)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Alspac ; Egea ; Gabriela ; Gwas ; Slsj ; Asthma ; Co-morbidity ; Eczema ; Phenotypic Heterogeneity
Sprache
englisch
Veröffentlichungsjahr
2022
HGF-Berichtsjahr
2022
ISSN (print) / ISBN
0954-7894
e-ISSN
1365-2222
Zeitschrift
Clinical & Experimental Allergy
Quellenangaben
Band: 52,
Heft: 1,
Seiten: 70-81
Verlag
Wiley
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Asthma and Allergy Prevention (IAP)
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Allergy
PSP-Element(e)
G-503300-001
Förderungen
Wellcome Trust
Medical Research Council
Medical Research Council
PubMed ID
34155719
Erfassungsdatum
2023-02-03