Association of WNT16 and FAM3C SNPs with Bone and Muscle Phenotypes in Young Adults
2019
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Poster Description
Peak bone mineral density (BMD) acquired in adolescence is postulated to be a predictor of future risk of osteoporosis and bone health disease. Studies have shown single-nucleotide polymorphisms (SNPs) at the WNT16 locus influence total BMD. One study demonstrated that polymorphisms in rs3801387 on WNT16 and rs917727 on the nearby FAM3C gene are associated with lower BMD. The purpose of this study is to explore musculoskeletal phenotypes associated with rs917727 and rs3801387 in three cohorts of children and young adults. The Applied Biosystems Taqman allelic discrimination assays and the QuantStudio 7 Flex Real-Time PCR system were used to genotype samples from the three cohorts. After being tested for Hardy-Weinberg equilibrium (HWE), the data was stratified by sex. Genotype-phenotype association was analyzed using analysis of covariance (ANCOVA) with an additive model. Where appropriate, post hoc pair-wise comparisons were performed and adjusted for multiple comparisons via Sidak method. Analysis demonstrated a significant association between variants in rs917727 and baseline isometric strength in both non-dominant (ND) (p=0.0469) and dominant (D) (p=0.022) arms, and one-repetition maximum (1-RM) strength in the D arm (p=0.0271) of males in an exercise cohort. Analysis of rs3801387 variants demonstrated significant associations with baseline isometric strength (p=0.027 ND arm, p=0.0341 D arm) in the same group. In a pediatric fracture cohort, rs3801387 variants were associated with total body BMD in males only (p=0.0388) but lumbar BMD among males (p=0.0300) and females (p=0.0388). This study supports prior results suggesting that variants of WNT16 rs3801387 are associated with lower BMD in males, but not females. This suggests a sexually dimorphic role for this variant. We also found that variants for FAM3C rs917727 and WNT16 rs3801387 are associated with muscle strength phenotypes, consistent with the tight and complex relationship between muscle and bone.
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