Prioritization of candidate causal genes for asthma in susceptibility loci derived from UK Biobank.

ABSTRACT: To identify candidate causal genes of asthma, we performed a genome-wide association study (GWAS) in UK Biobank on a broad asthma definition (n = 56,167 asthma cases and 352,255 controls). We then carried out functional mapping through transcriptome-wide association studies (TWAS) and Mendelian randomization in lung (n = 1,038) and blood (n = 31,684) tissues. The GWAS reveals 72 asthma-associated loci from 116 independent significant variants (P_GWAS < 5.0E-8). The most significant lung TWAS gene on 17q12-q21 is GSDMB (P_TWAS = 1.42E-54). Other TWAS genes include TSLP on 5q22, RERE on 1p36, CLEC16A on 16p13, and IL4R on 16p12, which all replicated in GTEx lung (n = 515). We demonstrate that the largest fold enrichment of regulatory and functional annotations among asthm

SUBMITTER: Valette K 

PROVIDER: S-EPMC8187656 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature