Unveiling genetic variants for age-related sarcopenia by conducting a genome-wide association study on Korean cohorts

Jin, Heejin; Yoo, Hyun Ju; Kim, Ye An; Lee, Ji Hyun; Lee, Young; Kwon, Seog Woon; Seo, Yoonho; Lee, Seung Hun; Koh, Jung‐Min; Ji, Yunmi; Ra, Ah; Won, Sungho; Seo, Je Hyun

doi:10.1038/s41598-022-07567-9

Cited by 11 publications

(13 citation statements)

References 54 publications

(66 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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The substantial decline in skeletal muscle mass, strength, and gait speed is a sign of severe sarcopenia, which may partly depend on genetic risk factors. So far, hundreds of genome-wide significant single nucleotide polymorphisms (SNPs) associated with handgrip strength, lean mass and walking pace have been identified in the UK Biobank cohort; however, their pleiotropic effects on all three phenotypes have not been investigated. By combining summary statistics of genome-wide association studies (GWAS) of handgrip strength, lean mass and walking pace, we have identified 78 independent SNPs (from 73 loci) associated with all three traits with consistent effect directions. Of the 78 SNPs, 55 polymorphisms were also associated with body fat percentage and 25 polymorphisms with type 2 diabetes (T2D), indicating that sarcopenia, obesity and T2D share many common risk alleles. Follow-up bioinformatic analysis revealed that sarcopenia risk alleles were associated with tiredness, falls in the last year, neuroticism, alcohol intake frequency, smoking, time spent watching television, higher salt, white bread, and processed meat intake; whereas protective alleles were positively associated with bone mineral density, serum testosterone, IGF1, and 25-hydroxyvitamin D levels, height, intelligence, cognitive performance, educational attainment, income, physical activity, ground coffee drinking and healthier diet (muesli, cereal, wholemeal or wholegrain bread, potassium, magnesium, cheese, oily fish, protein, water, fruit, and vegetable intake). Furthermore, the literature data suggest that single-bout resistance exercise may induce significant changes in the expression of 26 of the 73 implicated genes in m. vastus lateralis, which may partly explain beneficial effects of strength training in the prevention and treatment of sarcopenia. In conclusion, we have identified and characterized 78 SNPs associated with sarcopenia and 55 SNPs with sarcopenic obesity in European-ancestry individuals from the UK Biobank.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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“…Recent studies have found that, in humans, the interacting protein NUDT3 of QPCTL is an important genetic biomarker of sarcopenia in elderly individuals. The locus of this gene is related to lipid and energy metabolism [ 25 ]. Therefore, we studied the correlation between the growth rate of F2 populations and multiallelic Indels of the QPCTL gene, and found that the multiallelic Indels were significantly correlated with the ADG at the two stages ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

QPCTL Affects the Daily Weight Gain of the F2 Population and Regulates Myogenic Cell Proliferation and Differentiation in Chickens

Ren

Lin

Yang

et al. 2022

Animals

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Molecular breeding can accelerate the process of animal breeding and improve the breeding efficiency. To date, many Indel molecular markers have been identified in livestock and poultry, but how Indels affect economic traits is not well understood. For molecular breeding, it is crucial to reveal the mechanism of action of Indels and to provide more accurate information. The purpose of this study was to investigate how the 52/224-bp multiallelic Indels of the chicken QPCTL promoter area affect the daily weight gain of chickens and the potential regulatory mechanism of the QPCTL gene. The analysis was conducted by association analysis, qPCR, dual-fluorescence assay and Western blotting. The results showed that Indels in the QPCTL promoter region were significantly associated with the daily weight gain in chickens and that QPCTL expression showed a decreasing trend in embryonic breast muscle tissues. Furthermore, QPCTL expression was significantly higher in breast muscle tissues of the AC genotype than in those of the AB and BB genotypes. Based on the transcriptional activity results, the pGL3-C vector produced more luciferase activity than pGL3-A and pGL3-B. In addition, overexpression of QPCTL promoted chicken primary myoblast (CPM) proliferation and inhibited differentiation. The results of this study suggest that Indels in the promoter region of the QPCTL gene may regulate the proliferation and differentiation of CPMs by affecting the expression of QPCTL, which ultimately affects the growth rate of chickens. These Indels have important value for the molecular breeding of chickens, and QPCTL can be used as a candidate gene to regulate and improve chicken growth and development.

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“…For the discovery phase, participants aged ≥ 65 years were enrolled in the 'Veterans Sarcopenia Study'. 13 They were Koreans who visited the Division of Endocrinology, Department of Internal Medicine, Veterans Health Service Medical Center (Seoul, Korea) to undergo comprehensive geriatric assessment between August 2020 and March 2021. Before the study, all participants completed questionnaires, including medical history, EuroQol Visual Analogue Scale (EQ-VAS), SARC-F (strength, assistance in walking, rising from a chair, climbing stairs, falls), muscle mass measurement, muscle strength test, and blood sampling.…”

Section: Study Participantsmentioning

confidence: 99%

“…10,11 In addition, metabolic biomarkers such as lower n-3 fatty acids or genetic marker-related to lipid metabolism such as NUDT3 were reported in Asian population studies. 12,13 However, the interpretation of the results is limited by the lack of large scale-replication studies and experimental data which may reveal mechanistic insights and provide valuable information for a better understanding of clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies on metabolomic biomarkers for sarcopenia have shown that plasma ceramides and lysophosphatidylcholine (LysoPC) are associated with gait speed according to the results of the Baltimore Longitudinal Study of Aging 10,11 . In addition, metabolic biomarkers such as lower n‐3 fatty acids or genetic marker‐related to lipid metabolism such as NUDT3 were reported in Asian population studies 12,13 . However, the interpretation of the results is limited by the lack of large scale‐replication studies and experimental data which may reveal mechanistic insights and provide valuable information for a better understanding of clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Fatty acid amides as potential circulating biomarkers for sarcopenia

Kim

Lee

Koh

et al. 2023

J cachexia sarcopenia muscle

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Background Sarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age. Given that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detection are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform experimental studies using metabolomics. Methods Plasma metabolites from 142 elderly men, comprising a sarcopenia group and an age-matched control group, were measured using global metabolome profiling. Muscle and plasma samples from an aging mouse model of sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted metabolome profiling. Based on these experimental results, fatty acid amides were quantified from human plasma as well as human muscle tissues. The association of fatty acid amide levels with sarcopenia parameters was evaluated. Results Global metabolome profiling showed that fatty acid amide levels were significantly different in the plasma of elderly men with sarcopenia (all Ps < 0.01). Consistent with these results in human plasma, targeted metabolome profiling in an aging mouse model of sarcopenia showed decreased levels of fatty acid amides in plasma but not in muscle tissue. In addition, the levels of fatty acid amides increased in cell lysates during muscle cell differentiation. Targeted metabolome profiling in men showed decreased docosahexaenoic acid ethanolamide (DHA EA) levels in the plasma (P = 0.016) but not in the muscle of men with sarcopenia. DHA EA level was positively correlated with sarcopenia parameters such as skeletal muscle mass index (SMI) and handgrip strength (HGS) (P = 0.001, P = 0.001, respectively). The area under the receiver-operating characteristic curve (AUC) for DHA EA level ≤ 4.60 fmol/μL for sarcopenia was 0.618 (95% confidence interval [CI]: 0.532-0.698). DHA EA level ≤ 4.60 fmol/μL was associated with a significantly greater likelihood of sarcopenia (odds ratio [OR]: 2.11, 95% CI: 1.03-4.30), independent of HGS. The addition of DHA EA level to age and HGS significantly improved the AUC from 0.620 to 0.691 (P = 0.0497). Conclusions Our study demonstrated that fatty acid amides are potential circulating biomarkers in elderly men with sarcopenia. DHA EA, in particular, strongly related to muscle mass and strength, can be a key metabolite to become a reliable metabolic biomarker for sarcopenia. Further research on fatty acid amides will provide insights into the metabolomic changes relevant to sarcopenia from an aging perspective.

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Unveiling genetic variants for age-related sarcopenia by conducting a genome-wide association study on Korean cohorts

Cited by 11 publications

References 54 publications

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

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

QPCTL Affects the Daily Weight Gain of the F2 Population and Regulates Myogenic Cell Proliferation and Differentiation in Chickens

Fatty acid amides as potential circulating biomarkers for sarcopenia

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