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

Margaritte-Jeannin, Patricia; Budu-Aggrey, Ashley; Ege, Markus; Madore, Anne-Marie; Linhard, Christophe; Mohamdi, Hamida; Mutius, Erika von; Granell, Raquel; Demenais, Florence; Laprise, Catherine; Bouzigon, Emmanuelle und Dizier, Marie-Helene (2021): Identification of OCA2 as a novel locus for the co-morbidity of asthma-plus-eczema. In: Clinical and Experimental Allergy, Bd. 52, Nr. 1: S. 70-81

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0954-7894
• Sprache: Englisch