We are analyzing https://link.springer.com/article/10.1007/s11357-022-00721-1.

Title:
Genes encoding agrin (AGRN) and neurotrypsin (PRSS12) are associated with muscle mass, strength and plasma C-terminal agrin fragment concentration | GeroScience
Description:
Although physiological data suggest that neuromuscular junction (NMJ) dysfunction is a principal mechanism underpinning sarcopenia, genetic studies have implicated few genes involved in NMJ function. Accordingly, we explored whether genes encoding agrin (AGRN) and neurotrypsin (PRSS12) were associated with sarcopenia phenotypes: muscle mass, strength and plasma C-terminal agrin fragment (CAF). PhenoScanner was used to determine if AGRN and/or PRSS12 variants had previously been implicated with sarcopenia phenotypes. For replication, we combined genotype from whole genome sequencing with phenotypic data from 6715 GenoFit participants aged 18–83 years. Dual energy X-ray absorptiometry assessed whole body lean mass (WBLM) and appendicular lean mass (ALM), hand dynamometry determined grip strength and ELISA measured plasma CAF in a subgroup (n = 260). Follow-up analyses included eQTL analyses, carrier analyses, single-variant and gene-burden tests. rs2710873 (AGRN) and rs71608359 (PRSS12) associate with muscle mass and strength phenotypes, respectively, in the UKBB (p = 8.9 × 10−6 and p = 8.4 × 10−6) and GenoFit cohort (p = 0.019 and p = 0.014). rs2710873 and rs71608359 are eQTLs for AGRN and PRSS12, respectively, in ≥ three tissues. Compared to non-carriers, carriers of rs2710873 had 4.0% higher WBLM and ALM (both p < 0.001), and 9.5% lower CAF concentrations (p < 0.001), while carriers of rs71608359 had 2.3% lower grip strength (p = 0.034). AGRN and PRSS12 are associated with muscle strength and mass in single-variant analyses, while PRSS12 has further associations with muscle strength in gene-burden tests. Our findings provide novel evidence of the relevance of AGRN and PRSS12 to sarcopenia phenotypes and support existing physiological data illustrating the importance of the NMJ in maintaining muscle health during ageing.
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pubmed, article, sarcopenia, muscle, strength, google, scholar, prss, agrn, data, caf, grip, agrin, mass, cas, phenotypes, genofit, study, plasma, central, variants, table, hand, nmj, ukbb, association, variant, expression, analyses, neuromuscular, studies, cohort, genetic, analysis, associations, skeletal, human, genes, carriers, levels, significantly, pratt, noncarriers, findings, potential, results, samples, performed, neurotrypsin, fragment,

Topics {✒️}

c-terminal agrin fragment article download pdf open access license cir-myo myology centre extracellular matrix/mitochondria pathway enzyme-linked immunosorbent assay body fat-free mass mann–whitney u-tests nhgri-ebi gwas catalogue human genotype-phenotype associations older multimorbid community-dwellers array-based genotype data genome-wide association study neurotrypsin-resistant agrin reverses elucidating gene-phenotype associations genome-wide meta-analysis motor unit size giuseppe de vito muscle cross-sectional area gene-based association analyses neurotrypsin-dependent agrin cleavage muscle strength-related phenotypes plasma caf concentration genes encoding agrin article pratt gene-based burden tests gene-burden results complement transcriptomic profile jedd pratt demonstrating hand-specific differences full access significant gene-burden tests underpinning mechanism driving increased neurotrypsin-dependent cleavage single-variant analysis revealed study combines original population-based linkage analyses gene-burden data obtained variant-phenotype associations identified significantly lower levels variant-phenotype associations obtained post-alignment quality control genuity science ireland privacy choices/manage cookies genome-wide repository skeletal muscle mass skeletal muscle regulation skeletal muscle fibrosis specific genes linked skeletal muscle health

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WebPage:
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         headline:Genes encoding agrin (AGRN) and neurotrypsin (PRSS12) are associated with muscle mass, strength and plasma C-terminal agrin fragment concentration
         description:Although physiological data suggest that neuromuscular junction (NMJ) dysfunction is a principal mechanism underpinning sarcopenia, genetic studies have implicated few genes involved in NMJ function. Accordingly, we explored whether genes encoding agrin (AGRN) and neurotrypsin (PRSS12) were associated with sarcopenia phenotypes: muscle mass, strength and plasma C-terminal agrin fragment (CAF). PhenoScanner was used to determine if AGRN and/or PRSS12 variants had previously been implicated with sarcopenia phenotypes. For replication, we combined genotype from whole genome sequencing with phenotypic data from 6715 GenoFit participants aged 18–83 years. Dual energy X-ray absorptiometry assessed whole body lean mass (WBLM) and appendicular lean mass (ALM), hand dynamometry determined grip strength and ELISA measured plasma CAF in a subgroup (n = 260). Follow-up analyses included eQTL analyses, carrier analyses, single-variant and gene-burden tests. rs2710873 (AGRN) and rs71608359 (PRSS12) associate with muscle mass and strength phenotypes, respectively, in the UKBB (p = 8.9 × 10−6 and p = 8.4 × 10−6) and GenoFit cohort (p = 0.019 and p = 0.014). rs2710873 and rs71608359 are eQTLs for AGRN and PRSS12, respectively, in ≥ three tissues. Compared to non-carriers, carriers of rs2710873 had 4.0% higher WBLM and ALM (both p < 0.001), and 9.5% lower CAF concentrations (p < 0.001), while carriers of rs71608359 had 2.3% lower grip strength (p = 0.034). AGRN and PRSS12 are associated with muscle strength and mass in single-variant analyses, while PRSS12 has further associations with muscle strength in gene-burden tests. Our findings provide novel evidence of the relevance of AGRN and PRSS12 to sarcopenia phenotypes and support existing physiological data illustrating the importance of the NMJ in maintaining muscle health during ageing.
         datePublished:2023-01-07T00:00:00Z
         dateModified:2023-01-07T00:00:00Z
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         license:http://creativecommons.org/licenses/by/4.0/
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         keywords:
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            Genes
            Neuromuscular junction
            Muscle strength
            Muscle mass
            Agrin
            Cell Biology
            Geriatrics/Gerontology
            Molecular Medicine
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ScholarlyArticle:
      headline:Genes encoding agrin (AGRN) and neurotrypsin (PRSS12) are associated with muscle mass, strength and plasma C-terminal agrin fragment concentration
      description:Although physiological data suggest that neuromuscular junction (NMJ) dysfunction is a principal mechanism underpinning sarcopenia, genetic studies have implicated few genes involved in NMJ function. Accordingly, we explored whether genes encoding agrin (AGRN) and neurotrypsin (PRSS12) were associated with sarcopenia phenotypes: muscle mass, strength and plasma C-terminal agrin fragment (CAF). PhenoScanner was used to determine if AGRN and/or PRSS12 variants had previously been implicated with sarcopenia phenotypes. For replication, we combined genotype from whole genome sequencing with phenotypic data from 6715 GenoFit participants aged 18–83 years. Dual energy X-ray absorptiometry assessed whole body lean mass (WBLM) and appendicular lean mass (ALM), hand dynamometry determined grip strength and ELISA measured plasma CAF in a subgroup (n = 260). Follow-up analyses included eQTL analyses, carrier analyses, single-variant and gene-burden tests. rs2710873 (AGRN) and rs71608359 (PRSS12) associate with muscle mass and strength phenotypes, respectively, in the UKBB (p = 8.9 × 10−6 and p = 8.4 × 10−6) and GenoFit cohort (p = 0.019 and p = 0.014). rs2710873 and rs71608359 are eQTLs for AGRN and PRSS12, respectively, in ≥ three tissues. Compared to non-carriers, carriers of rs2710873 had 4.0% higher WBLM and ALM (both p < 0.001), and 9.5% lower CAF concentrations (p < 0.001), while carriers of rs71608359 had 2.3% lower grip strength (p = 0.034). AGRN and PRSS12 are associated with muscle strength and mass in single-variant analyses, while PRSS12 has further associations with muscle strength in gene-burden tests. Our findings provide novel evidence of the relevance of AGRN and PRSS12 to sarcopenia phenotypes and support existing physiological data illustrating the importance of the NMJ in maintaining muscle health during ageing.
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      dateModified:2023-01-07T00:00:00Z
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      keywords:
         Sarcopenia
         Genes
         Neuromuscular junction
         Muscle strength
         Muscle mass
         Agrin
         Cell Biology
         Geriatrics/Gerontology
         Molecular Medicine
      image:
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      name:Anthony Ryan
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               type:PostalAddress
            type:Organization
      name:Thorhildur Juliusdottir
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            address:
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               type:PostalAddress
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            name:University of Padova
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               type:PostalAddress
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      name:Giuseppe De Vito
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            name:University of Padova
            address:
               name:Department of Biomedical Sciences, CIR-Myo Myology Centre, Neuromuscular Physiology Laboratory, University of Padova, Padua, Italy
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      name:Colin Boreham
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            address:
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PostalAddress:
      name:Institute for Sport and Health, University College Dublin, Dublin, Ireland
      name:Genuity Science, Dublin, Ireland
      name:Department of Biomedical Sciences, CIR-Myo Myology Centre, Neuromuscular Physiology Laboratory, University of Padova, Padua, Italy
      name:Genuity Science, Dublin, Ireland
      name:Genuity Science, Dublin, Ireland
      name:Genuity Science, Reykjavik, Iceland
      name:Genuity Science, Dublin, Ireland
      name:Genuity Science, Dublin, Ireland
      name:Department of Biomedical Sciences, CIR-Myo Myology Centre, Neuromuscular Physiology Laboratory, University of Padova, Padua, Italy
      name:Department of Biomedical Sciences, CIR-Myo Myology Centre, Neuromuscular Physiology Laboratory, University of Padova, Padua, Italy
      name:Institute for Sport and Health, University College Dublin, Dublin, Ireland

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