Targeted genotype analyses of GWAS-derived lean body mass and handgrip strength-associated single nucleotide polymorphisms in elite masters athletes

Recent large genome-wide association studies (GWAS) have independently identified a set of genetic loci associated with lean body mass (LBM) and handgrip strength (HGS). Evaluation of these candidate single nucleotide polymorphisms (SNPs) may be useful to investigate genetic traits of populations at higher or lower risk of muscle dysfunction. As such, we investigated associations between six SNPs linked to LBM or HGS, in a population of elite master athletes (MA), and age-matched controls, as a representative population of older individuals with variable maintenance of muscle mass and function. Genomic DNA was isolated from buffy coat samples of 96 individuals (consisting of 48 MA (71±6yrs; age-graded performance 83±9%) and 48 older controls (75±6yrs)). SNP validation and sample genotyping was conducted using the tetra-primer amplification refractory mutation system (ARMS). For the 3 SNPs analysed that were previously associated with LBM (FTO, IRS1 and ADAMTSL3), multinomial logistic regression revealed a significant association of the ADAMTSL3 genotype with %LBM (P [less than] 0.01). For the three HGS-linked SNPs, neither GBF1 nor GLIS1 showed any association with HGS, but for TGFA, multinomial logistic regression revealed a significant association of genotype with HGS (P [less than] 0.05). For ADAMTSL3, there was an enrichment of the effect allele in the MA (P [less than] 0.05; Fisher's exact test). Collectively, of the six SNPs analysed, ADAMTSL3 and TGFA showed significant associations with LBM and HGS, respectively. The functional relevance of the ADAMTSL3 SNP in body composition, and of TGFA in strength, may highlight a genetic component of the elite MA phenotype