Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual.

ABSTRACT:

Background

Bone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this dynamic phenotype by modeling longitudinal bone accrual across 11,000 bone scans in a cohort of healthy children and adolescents, followed by genome-wide association studies (GWAS) and variant-to-gene mapping with functional follow-up.

Results

We identify 40 loci, 35 not previously reported, with various degrees of supportive evidence, half residing in topological associated domains harboring known bone genes. Of several loci potentially associated with later-life fracture risk, a candidate SNP lookup provides the most compelling evidence for rs11195210 (SMC3)

SUBMITTER: Cousminer DL 

PROVIDER: S-EPMC7780623 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature