CYP11B1 variants influence skeletal maturation via alternative splicing.

ABSTRACT: We performed genome-wide association study meta-analysis to identify genetic determinants of skeletal age (SA) deviating in multiple growth disorders. The joint meta-analysis (N = 4557) in two multiethnic cohorts of school-aged children identified one locus, CYP11B1 (expression confined to the adrenal gland), robustly associated with SA (rs6471570-A; β = 0.14; P = 6.2 × 10^-12). rs6410 (a synonymous variant in the first exon of CYP11B1 in high LD with rs6471570), was prioritized for functional follow-up being second most significant and the one closest to the first intron-exon boundary. In 208 adrenal RNA-seq samples from GTEx, C-allele of rs6410 was associated with intron 3 retention (P = 8.11 × 10^-40), exon 4 inclusion (P = 4.29 × 10^-34), and decreased exo

SUBMITTER: Grgic O 

PROVIDER: S-EPMC8578655 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature