Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

Willems, Sara M.; Wright, Deil S.; Day, Felix R.; Trajanoska, Katerina; Joshi, Peter K.; Morris, John A.; Matteini, Amy M.; Garton, Fleur; Grarup, Niels; Oskolkov, Nikolay; Thalamuthu, Anbupalam; Mangino, Massimo; Liu, Jun; Demirkan, Ayşe; Lek, Monkol; Xu, Li‐Wen; Wang, Guan; Oldmeadow, Christopher; Gaulton, Kyle J.; Lotta, Luca A.; Miyamoto‐Mikami, Eri; Rivas, Manuel A.; White, Tom; Loh, Po−Ru; Aadahl, Mette; Amin, Najaf; Attia, John; Austin, Krista G.; Benyamin, Beben; Brage, Sören; Cheng, Yu‐Ching; Cięszczyk, Paweł; Derave, Wim; Eriksson, Karl-Fredrik; Eynon, Nir; Linneberg, Allan; Lucía, Alejandro; Massidda, Myosotis; Mitchell, Braxton D.; Miyachi, Motohiko; Murakami, Haruka; Padmanabhan, Sandosh; Pandey, Ashutosh Kumar; Papadimitriou, Ioannis; Rajpal, Deepak K.; Sale, Craig; Schnurr, Theresia M.; Sessa, Francesco; Shrine, Nick; Tobin, Martin D.; Varley, Ian; Wain, Louise V.; Wray, Naomi R.; Lindgren, Cecilia M.; MacArthur, Daniel G.; Waterworth, Dawn; McCarthy, Mark I.; Pedersen, Oluf; Khaw, Kay‐Tee; Kiel, Douglas P.; Pitsiladis, Yannis; Fuku, Noriyuki; Franks, Paul W.; North, Klaus; Duijn, Cornelia M. van; Mather, Karen A.; Hansen, Torben; Hansson, Ola; Spector, Tim D.; Murabito, Joanne M.; Richards, J. Brent; Rivadeneira, Fernando; Langenberg, Claudia; Perry, John R. B.; Wareham, Nick; Scott, Robert A.

doi:10.1038/ncomms16015

Cited by 172 publications

(178 citation statements)

References 69 publications

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“…[102][103][104] One study used global mRNA sequencing to detect genes that were upregulated in human skeletal muscle as an outcome of acute and/or long-term exercise. 102,105 For example, some studies have examined relationships between SNPs and muscle strength in GWAS studies. 103 Some transcripts encode well-known myokines, such as irisin, BDNF and IL-6, which have been described extensively and are reviewed elsewhere, 2,3,5,102-104 ; others have not been studied previously in skeletal muscle and may encode novel myokines.…”

Section: Myokines As Biomarkersmentioning

confidence: 99%

“…103 Some transcripts encode well-known myokines, such as irisin, BDNF and IL-6, which have been described extensively and are reviewed elsewhere, 2,3,5,102-104 ; others have not been studied previously in skeletal muscle and may encode novel myokines. 102,105 For example, ACTG1 knockout mice demonstrate muscle weakness as well as whole-body functional deficits. 102,105 For example, some studies have examined relationships between SNPs and muscle strength in GWAS studies.…”

Section: Myokines As Biomarkersmentioning

confidence: 99%

“…102,103 In addition, Genome-wide association studies (GWAS) have been instrumental in the identification of a multitude of pleiotropic candidate single-nucleotide polymorphisms (SNPs)/loci associated with traits related to skeletal muscle physiology and metabolism, with multiple loci overlapping between the traits. 102,105 Moreover, three lead SNPs (rs10186876, rs6687430 and rs754512) for grip strength were located near genes implicated in monogenic syndromes characterized by psychomotor and/or neurological impairment. Muscle strength, measured by isometric hand grip strength, is a widely used proxy of muscular fitness, an established marker of frailty, and predictor of physical decline and functional impairments.…”

Section: Myokines As Biomarkersmentioning

confidence: 99%

“…102,105 For example, some studies have examined relationships between SNPs and muscle strength in GWAS studies. 102,105 The characterization of these loci via genetic and functional work will help elucidate new pathways involved in the regulation of muscle strength and suggest new strategies to tackle muscle wasting. Higher grip strength has been found to be prognostic of recovery after hip fracture surgery while lower grip strength is associated with the reduced quality of life in the ageing population.…”

Section: Myokines As Biomarkersmentioning

confidence: 99%

“…Muscle strength, measured by isometric hand grip strength, is a widely used proxy of muscular fitness, an established marker of frailty, and predictor of physical decline and functional impairments. 102,105 Continuation of this line of research is likely to provide additional information as to expression how different myokines is regulated, and how expression levels correlate with muscle physiology and metabolism. 102 discovered that a number of these loci were located within or close to genes implicated in structure and function of skeletal muscle fibres (ACTG1), involvement in the regulation of neurotransmission (PEX14, TGFA and SYT1), excitation-contraction coupling (SLC8A1) or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1).…”

Section: Myokines As Biomarkersmentioning

confidence: 99%

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Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

2019

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Myokines are molecules produced and secreted by skeletal muscle to act in an auto-, para-and endocrine manner to alter physiological function of target tissues. The growing number of effects of myokines on metabolism of distant tissues provides a compelling case for crosstalk between skeletal muscle and other tissues and organs to regulate metabolic homoeostasis. In this review, we summarize and discuss the current knowledge regarding the impact on metabolism of several canonical and recently identified myokines. We focus specifically on myostatin, β-aminoisobutyric acid, interleukin-15, meteorin-like and myonectin, and discuss how these myokines are induced and regulated as well as their overall function. We also review how these myokines may serve as potential prognostic biomarkers that reflect whole-body metabolism and how they may be attractive therapeutic targets for treating muscle and metabolic diseases. K E Y W O R D Sinterleukin-15, metabolism, meteorin-like, myonectin, myostatin, β-aminoisobutyric acid

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Section: Myokines As Biomarkersmentioning

confidence: 99%

Section: Myokines As Biomarkersmentioning

confidence: 99%

Section: Myokines As Biomarkersmentioning

confidence: 99%

Section: Myokines As Biomarkersmentioning

confidence: 99%

Section: Myokines As Biomarkersmentioning

confidence: 99%

See 3 more Smart Citations

Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

2019

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Genetics of somatotype and physical fitness in children and adolescents

Silventoinen

Maia

Jelenkovic

et al. 2020

American J Hum Biol

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Objectives To analyze the influence of genetic and environmental factors on the variation in somatotype, physical fitness, and their mutual associations. Methods Twins from 214 pairs (87 monozygotic) of the Autonomous Region of Madeira, Portugal, from 3 to 18 years of age (51% girls) were assessed in anthropometry and physical fitness tests. We estimated endomorphy, mesomorphy, and ectomorphy based on anthropometric measures and physical fitness using the Eurofit test battery. Two age categories were analyzed: children (3‐11 years) and adolescents (12‐18 years). Genetic and environmental variations were estimated using quantitative genetic twin modeling. Results No genetic sex differences were found, thus boys and girls were pooled in all genetic analyses. Heritability estimates were high for somatotype (a2 = 0.80‐0.93), physical fitness traits (a2 = 0.67‐0.83), and largely similar in children and adolescents. Positive correlations were found for ectomorphy with motor ability and cardiorespiratory endurance as well as for endomorphy and mesomorphy with muscular strength (r = 0.25‐0.37). In contrast, negative associations were found for ectomorphy with muscular strength, as well as for endomorphy and mesomorphy with motor ability and cardiorespiratory endurance (−0.46 to −0.26). Twin modeling indicated that these associations were explained mostly by genetic factors in common to the two associated traits (84% or more). Conclusions Associations between somatotype and physical fitness tests are mainly explained by common genetic background in children and adolescents. Therefore, interventions in youth should consider that a child's performance in physical fitness tests partly reflects their inherited physique.

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Athletes in sporting events with upper‐body gripping movements have greater handgrip strength than those in sporting events that prioritize the lower body

Abe

Kohmura

Suzuki

et al. 2023

American J Hum Biol

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Objective Evidence suggests that acquiring a high level of handgrip strength early in life and maintaining that strength throughout life may be important for health. In addition, it is thought that sports activities performed during the developmental period are effective in improving handgrip strength, but it is unknown what types of sports are more effective. As a first step, we conducted a cross‐sectional study to compare handgrip strength across different sports (upper‐body gripping sports vs. lower body) in early adulthood. Methods We used the Juntendo Fitness Plus Study data from 1973 to 2018 and selected two types of sporting events with matching physiques (soccer, baseball, and kendo) but different degrees of gripping. Data on 7344 male first‐year sports university students included 1127 soccer, 297 Kendo, and 698 baseball players. Results Those in the lower body‐only (soccer) sports had −3.78 (95% CI: −4.27, −3.29) kg lower handgrip strength than those in the lower + upper (kendo and baseball). Comparing each individual sport found that each sport was different from each other with Kendo > Baseball > Soccer (between each sport, p < .001). In addition, the difference between sports has become greater across time. Conclusions In early adulthood, handgrip strength is greatest in those participating in sports with upper‐body movements compared to those participating in sports that mainly involved lower‐body movements. The three sports we selected are natural activities that do not directly train handgrip strength. Therefore, sport may be one potential method to improve low handgrip strength in children/adolescents during the developmental period.

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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness

Cited by 172 publications

References 69 publications

Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

Genetics of somatotype and physical fitness in children and adolescents

Athletes in sporting events with upper‐body gripping movements have greater handgrip strength than those in sporting events that prioritize the lower body

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