Polygenic Models Partially Predict Muscle Size and Strength but Not Low Muscle Mass in Older Women

Abstract

Background: Heritability explains 45-82% of muscle mass and strength variation, yet polygenic models for muscle phenotypes in older women are scarce. Therefore, the objective of the present study was to (1) assess if total genotype predisposition score (GPSTOTAL) for a set of polymorphisms differed between older women with low and high muscle mass, and (2) utilise a data-driven GPS (GPSDD) to predict the variance in muscle size and strength-related phenotypes. Methods: In three-hundred 60- to 91-year-old Caucasian women (70.7 ± 5.7 years), skeletal muscle mass, biceps brachii thickness, vastus lateralis anatomical cross-sectional area (VLACSA), hand grip strength (HGS), and elbow flexion (MVCEF) and knee extension (MVCKE) maximum voluntary contraction were measured. Participants were classified as having low muscle mass if the skeletal muscle index (SMI) < 6.76 kg/m2 or relative skeletal muscle mass (%SMMr) < 22.1%. Genotyping was completed for 24 single-nucleotide polymorphisms (SNPs). GPSTOTAL was calculated from 23 SNPs and compared between the low and high muscle mass groups. A GPSDD was performed to identify the association of SNPs with other skeletal muscle phenotypes. Results: There was no significant difference in GPSTOTAL between low and high muscle mass groups, irrespective of classification based on SMI or %SMMr. The GPSDD model, using 23 selected SNPs, revealed that 13 SNPs were associated with at least one skeletal muscle phenotype: HIF1A rs11549465 was associated with four phenotypes and, in descending number of phenotype associations, ACE rs4341 with three; PTK2 rs7460 and CNTFR rs2070802 with two; and MTHFR rs17421511, ACVR1B rs10783485, CNTF rs1800169, MTHFR rs1801131, MTHFR rs1537516, TRHR rs7832552, MSTN rs1805086, COL1A1 rs1800012, and FTO rs9939609 with one phenotype. The GPSDD with age included as a predictor variable explained 1.7% variance of biceps brachii thickness, 12.5% of VLACSA, 19.0% of HGS, 8.2% of MVCEF, and 9.6% of MVCKE. Conclusions: In older women, GPSTOTAL did not differ between low and high muscle mass groups. However, GPSDD was associated with muscle size and strength phenotypes. Further advancement of polygenic models to understand skeletal muscle function during ageing might become useful in targeting interventions towards older adults most likely to lose physical independence.

Association of Gene Variants for Mechanical and Metabolic Muscle Quality with Cardiorespiratory and Muscular Variables Related to Performance in Skiing Athletes

“…Here, we identified an effect of the assessed ACE and Tenascin polymorphism on cardiovascular parameters. At the skeletal muscle level, strong effects of the studied genotypes on ACTN3, PTK2 and ACE was detected based on effect sizes > 0.1, which contrasts with previous findings [ 24 , 25 , 36 , 37 ]. Our observations emphasize that discrete and considerable associations exist for distinct elements of genetic variation and parameters of the performance phenotype.…”

Genetic polymorphisms of muscular fitness in young healthy men

“…Finally, while the study population used in the current study is smaller than that used in some association-seeking studies, it is not of unusual sample size of many other similar studies [ 62 , 63 ]. In fact, the sample size was adequate to detect significant, and hence physiologically meaningful, associations, and one may query the physiological significance of any additional association if it can only be detected with investigating very large populations.…”

Identification and Characterization of Genomic Predictors of Sarcopenia and Sarcopenic Obesity Using UK Biobank Data

“…Several studies have investigated the association between the DNA polymorphisms and sarcopenia-related traits outside of the UK Biobank project using GWAS [ 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ] or a candidate gene [ 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ] approaches. Apart from the classical skeletal muscle traits (lean mass, absolute and relative skeletal muscle mass, skeletal muscle mass index, muscle thickness, anatomical cross-sectional area of muscle groups, etc.…”