1. Identification of OCA2 as a novel locus for the co-morbidity of asthma-plus-eczema.
- Author
-
Margaritte-Jeannin P, Budu-Aggrey A, Ege M, Madore AM, Linhard C, Mohamdi H, von Mutius E, Granell R, Demenais F, Laprise C, Bouzigon E, and Dizier MH
- Subjects
- Comorbidity, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Membrane Transport Proteins genetics, Morbidity, Albinism, Oculocutaneous, Asthma epidemiology, Asthma genetics, Eczema epidemiology, Eczema genetics, Rhinitis, Allergic epidemiology, Rhinitis, Allergic genetics
- Abstract
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., (© 2021 John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF