In the first genome-wide association analysis to focus on SNP-by-sex interaction for various different bone mineral density (BMD) phenotypes, Liu et al. initially identified 12 SNP–sex interaction loci that appeared to have the potential to show genome-wide significance.
The 12 SNPs included a novel genome-wide significant interaction that was associated with lumbar spine BMD near to the GRM7 gene at Chr3p26.1−p25.1 (male effect=0.02 and p=3.0 × 10
The researchers then checked the SNP-by-sex interactions identified against the largest meta-analysis of genome-wide association studies done to date but did not find any significant associations.
Editor’s comment: Liu and colleagues report that, despite the large collaborative effort (more than 50,000 men and women), no genome-wide significant evidence for gene-by-sex interaction was found influencing BMD variation. This suggests that we need to look beyond differences in common autosomal SNPs and focus on coding and regulatory regions. More sexually dimorphic bone traits (such as bone geometry, microarchitecture, and fracture, per se), may be best explored by genome-wide interaction studies such as this.