Regulatory elements in <i>SEM1-DLX5-DLX6</i> (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits.

ABSTRACT:

Purpose

The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown.

Methods

We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model.

Results

Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.3 SEM1-DLX5-DLX6 locus, and their combination conferred over 7-fold increased risk of cNCS. The top variants were replicated in an independent cohort and showed pleiotropic effects on brain and facial morphology and bone mineral density. Fine mapping of 7q21.3 identif

SUBMITTER: Nicoletti P 

PROVIDER: S-EPMC11434253 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature