Fig. 3.

Genome-wide association and variant-to-gene mapping highlight three loci associated with pediatric bone accrual. a Overview of variant-to-gene mapping pipeline. We first identify all SNPs in high LD with our sentinel associated variant. These are then filtered by residing in open chromatin as assessed by ATAC-seq in hMSC-derived osteoblasts. The open chromatin variants are subsequently filtered by being in direct physical contact with gene promoter baits. Finally, siRNA knockdown experiments are performed for a subset of these contacted genes to assess the impact on osteogenesis. b Locus plot for signal 1, near CC2D1B, showing the association landscape with key SNPs marked, chromatin accessibility as assessed by ATAC-seq and Promoter CaptureC interaction loops, the locations of all proxy SNPs in the region, and the locations of genes at this locus, with the four genes followed up with in vitro functional analysis highlighted in yellow. c Forest plots showing the association results in each subsample (Black and Non-Black males and females). d Representative mean SITAR curves by genotype for rs2762826. Complete variant-to-gene mapping results are given in Additional file 1: Table S16