Fig. 4

Functional characterization of rs146662075 association signal. a Signal plot for X chromosome region surrounding rs146662075. Each point represents a variant, with its p-value (on a −log10 scale, y axis) derived from the meta-analysis results from association testing in males. The x axis represents the genomic position (hg19). Below, representation of H3K27ac and RNA-seq in a subset of cell types is shown. The association between RNA-seq signals and H3K27ac marks suggests that AGTR2 is the most likely regulated gene by the enhancer that harbors rs146662075. b The presence of the common allelic variant rs146662075-C reduces enhancer activity in luciferase assays performed in a mouse myoblast cell line. c Electrophoretic mobility shift assay in C2C12 myoblast cell lines, C2C12-differentiated myotubes, and human fetal myoblasts showed allele-specific binding of a ubiquitous nuclear complex. The arrows indicate the allele-specific binding event. Competition was carried out using 50- and 100-fold excess of the corresponding unlabeled probe