Single Nucleotide Polymorphisms in CLDN14 and SMOC1 Affecting Bone Mineral Density Influence Other Musculoskeletal Traits

Background: A recent genome-wide association study (GWAS) identified novel genes influencing bone mineral density (BMD). This three stage GWAS identified two novel loci: rs227425 in the SPARC-Related Modular Calcium Binding 1 gene (SMOC1) was significantly associated with BMD and rs170183 in the claudin 14 (CLDN14) gene was significantly associated with BMD in females. Objective: The purpose of this study was to determine if two novel single nucleotide polymorphisms (SNPs) known to affect BMD are associated with other musculoskeletal traits. Methods/Design :The Bone Health Cohort consists of 150 African-American participants enrolled at Children’s National Health System as part of a fracture analysis study. The FAMuSS study examined young adults who volunteered for 12-week unilateral resistance training of the non-dominant arm. SNPs were genotyped in both cohorts using a TaqMan allelic discrimination assay. Associations between SNPs and phenotypes were tested using ANCOVA using age and sex as covariates. Significant associations were then analyzed via t-test to identify significance between individual genotypes. Results/Discussion: Our findings extend the influence of the CLDN14 gene beyond BMD and suggest its novel role in muscular responsivity to exercise among young adults and in fat mass among African American children. Our results also indicate sexual dimorphism in the effect of CLDN14 on muscle response to exercise. These findings could be used to identify individuals at risk for sarcopenia as well as proliferation of fat mass. Findings from the Bone Health Cohort implicate a novel role for the SMOC1 gene in fat mass among female and male African American children. No direct association between SMOC1 and fat mass has been identified prior to this study. In parallel with findings from the Bone Health Cohort in the CLDN14 gene, results regarding SMOCI in this cohort may promote identification of those at risk for fat mass accumulation in childhood, especially among a group at risk for obesity.