Association between polygenetic risk scores related to sarcopenia risk and their interactions with regular exercise in a large cohort of Korean adults

Abstract

Background & aims: Sarcopenia elevates metabolic disorders in the elderly, and genetic and environmental factors influence the risk of sarcopenia. The purpose of the study was to examine the hypothesis that polygenetic variants for sarcopenic risk had interactions with metabolic disorders and lifestyles associated with sarcopenia risk in adults >50 years in a large urban hospital cohort.

Methods: Sarcopenia was defined as an appendicular skeletal muscle mass/body weight (SMI) < 29.0% for men and <22.8% for women estimated from participants aged 18-39 years in the KNHANES 2009-2010. Genetic variants were selected using a genome-wide association study for sarcopenia (sarcopenia, n = 1368; control, n = 15,472). The best model showing the gene-gene interactions was selected using a generalized multifactor dimensionality reduction. The polygenic risk scores (PRS) were generated by summing the selected SNP risk alleles in the best model.

Results: SMI was much higher in the control subjects than the sarcopenia subjects in both genders, and the fat mass index was opposite the SMI. The five-single nucleotide polymorphisms (SNPs) model included FADS2_rs97384, MYO10_rs31574 KCNQ5_rs6453647, DOCK5_rs11135857, and LRP1B_ rs74659977. Sarcopenia risk was positively associated with the PRS of the five-SNP model (ORs = 1.977, 95% CI = 1.634-2.393). The PRS interacted with age (P < 0.0001), metabolic syndrome (P = 0.01), grip strength (P = 0.007), and serum total cholesterol concentrations (P = 0.005) for the sarcopenia risk. There were no interactions of PRS with the lifestyle components except for exercise.

Conclusion: The genetic impact may be offset in the elderly, having metabolic syndrome, high serum total cholesterol concentrations, and high grip strength, but only exercise in the lifestyle factors can overcome the genetic effect. Middle-aged and elderly participants with a genetic risk for sarcopenia may require regular exercise to maintain high grip strength and prevent metabolic syndrome.

Keywords: Fat mass; Grip strength; Metabolic syndrome; Polygenetic risk scores; Sarcopenia; Skeletal muscle mass.