Large-scale, multiethnic genome-wide association study identifies novel loci contributing to asthma susceptibility in adults

• Published in: Journal of allergy and clinical immunology 2019-04, Vol.143 (4), p.1633-1635
• Main Authors: Dahlin, Amber, Sordillo, Joanne E., Ziniti, John, Iribarren, Carlos, Lu, Meng, Weiss, Scott T., Tantisira, Kelan G., Lu, Quan, Kan, Mengyuan, Himes, Blanca E., Jorgenson, Eric, Wu, Ann Chen
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Adult; African Americans; Asthma; Asthma - ethnology; Asthma - genetics; Binding sites; Chromosome 2; Chromosome 6; Chromosomes; Female; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype; Hispanic people; Humans; Interleukin 1; Male; Minority & ethnic groups; Phenotypes; Polymorphism, Single Nucleotide; Quality control; Respiratory tract; Single-nucleotide polymorphism; Studies
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2018.11.037

[...]characterization of rs12712142, which was annotated to the 3'UTR region of IL1RL1, showed that it introduces a new binding site for hsa-miR-452-5p, which is also significantly upregulated in airway epithelia samples from those with asthma compared with samples from healthy, nonatopic controls (see Figs E2 and E3 in this article's Online Repository at www.jacionline.org). Because variations across multiple genes within affected pathways could directly impact asthma phenotypes, we analyzed 2143 suggestive (P < 1 × 10−05) associations from non-Hispanic whites in GERA for gene-set and tissue enrichment. Collectively, these analyses replicated previously reported top asthma GWAS findings as well as increased the significance threshold for many of these associations, in addition to expanding the list of novel SNPs that are strongly associated with asthma risk. Because of differences in GWAS study design, imputation, and available SNP data, most genome-wide significant SNPs from the discovery GWAS were not well represented in EVE or GABRIEL, limiting the total number of SNPs for replication. [...]although we present novel GWAS findings from racial/ethnic groups in addition to non-Hispanic whites, our ability to replicate associations from these and other populations was limited, due in part to the aforementioned reasons. [...]previously unreported SNPs within the MHC II region of chromosome 6 and the IL1RL1/IL18R1 region of chromosome 2 are associated with asthma susceptibility in adults of non-Hispanic white ancestry, whereas novel SNPs in FOXRED2 and TXN2 are associated with asthma in Asians, and COL3A1 is associated with asthma in African Americans.