Altered pubertal timing in 7q11.23 copy number variations and associated genetic mechanisms.

ABSTRACT: Pubertal timing, including age at menarche (AAM), is a heritable trait linked to lifetime health outcomes. Here, we investigate genetic mechanisms underlying AAM by combining genome-wide association study (GWAS) data with investigations of two rare genetic conditions clinically associated with altered AAM: Williams syndrome (WS), a 7q11.23 hemideletion characterized by early puberty; and duplication of the same genes (7q11.23 Duplication syndrome [Dup7]) characterized by delayed puberty. First, we confirm that AAM-derived polygenic scores in typically developing children (TD) explain a modest amount of variance in AAM (R² = 0.09; p = 0.04). Next, we demonstrate that 7q11.23 copy number impacts AAM (WS < TD < Dup7; p = 1.2x10^-8, η² = 0.45) and pituitary volu

SUBMITTER: Wei SM 

PROVIDER: S-EPMC10875153 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature