{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:25:41Z","timestamp":1787135141485,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Sarcopenia is a multidimensional musculoskeletal-aging phenotype defined by reduced muscle quantity together with weakness and impaired performance, but public genetic resources rarely capture sarcopenia as a single uniformly labeled phenotype. Methods: Official National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) genome-wide association studies (GWAS) Catalog association files archived locally on 15 April 2026 were grouped into muscle-quantity and function-frailty domains. Exact shared rsIDs were identified, assigned to catalog representative\/mapped genes, evaluated against exploratory skeletal-muscle transcriptomic context, benchmarked with trait-grouping sensitivity analyses, and ranked with a secondary multi-criteria evidence-integration framework. Results: The muscle-quantity domain contained 1580 unique single-nucleotide polymorphisms (SNPs) and the function-frailty domain contained 383 unique SNPs, with 14 exact rsIDs shared between domains. A trait-file permutation benchmark did not show that this overlap exceeded a catalog-level null expectation (empirical p = 0.514), so the shared set is interpreted as a descriptive, high-specificity candidate intersection rather than statistically enriched sharing. Sensitivity analyses showed that the 14-rsID set was retained after excluding falling\/fall and chronic obstructive pulmonary disease (COPD)-related proxy traits, indicating that the primary shared set was driven mainly by grip\/low-grip function traits. Exploratory transcriptomic context and evidence integration organized candidates for follow-up but did not validate causal or linkage disequilibrium (LD)-level sharing. Conclusions: This framework generates candidate hypotheses for sarcopenia-related musculoskeletal aging but does not establish causal, fine-mapped, or statistically enriched genetic sharing.<\/jats:p>","DOI":"10.3390\/life16081357","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:30:53Z","timestamp":1787131853000},"page":"1357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative GWAS Catalog Analysis of Proxy-Trait Intersection in Sarcopenia-Related Musculoskeletal Aging with Multi-Criteria Evidence Integration"],"prefix":"10.3390","volume":"16","author":[{"given":"Hung-Wen","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Applied Science and Engineering, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Long","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Applied Science and Engineering, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Jen","family":"Liang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Applied Science and Engineering, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6381-4269","authenticated-orcid":false,"given":"Yen-Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical University, New Taipei City 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"afac220","DOI":"10.1093\/ageing\/afac220","article-title":"Sarcopenia definition, diagnosis and treatment: Consensus is growing","volume":"51","author":"Sayer","year":"2022","journal-title":"Age Ageing"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.3346\/jkms.2022.37.e146","article-title":"A Review of Sarcopenia Pathophysiology, Diagnosis, Treatment and Future Direction","volume":"37","author":"Cho","year":"2022","journal-title":"J. Korean Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155533","DOI":"10.1016\/j.metabol.2023.155533","article-title":"Epidemiology of sarcopenia: Prevalence, risk factors, and consequences","volume":"144","author":"Yuan","year":"2023","journal-title":"Metabolism"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4989","DOI":"10.3892\/ijmm.2021.4989","article-title":"Pathophysiology and mechanisms of primary sarcopenia (Review)","volume":"48","author":"Nishikawa","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"155638","DOI":"10.1016\/j.metabol.2023.155638","article-title":"Sarcopenia, osteoporosis and frailty","volume":"145","author":"Gielen","year":"2023","journal-title":"Metabolism"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101270","DOI":"10.1016\/j.mam.2024.101270","article-title":"Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies","volume":"97","author":"Liu","year":"2024","journal-title":"Mol. Asp. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Feng, Z., Xia, J., Yu, J., Wang, J., Yin, S., Yang, J., Wu, T., Zhang, Z., Yan, W., and Wang, S. (2025). Pathophysiological Mechanisms Underlying Sarcopenia and Sarcopenic Obesity: A Systematic Review and Meta-Analysis of Biomarker Evidence. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115113"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"D977","DOI":"10.1093\/nar\/gkac1010","article-title":"The NHGRI-EBI GWAS Catalog: Knowledgebase and deposition resource","volume":"51","author":"Sollis","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41467-017-00031-7","article-title":"Large meta-analysis of genome-wide association studies identifies five loci for lean body mass","volume":"8","author":"Zillikens","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.ajhg.2019.10.014","article-title":"Genome-wide Associations Reveal Human-Mouse Genetic Convergence and Modifiers of Myogenesis, CPNE1 and STC2","volume":"105","author":"Gonzales","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s42003-020-01334-0","article-title":"The genetic architecture of appendicular lean mass characterized by association analysis in the UK Biobank study","volume":"3","author":"Pei","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16015","DOI":"10.1038\/ncomms16015","article-title":"Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness","volume":"8","author":"Willems","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6451","DOI":"10.1038\/s41598-018-24735-y","article-title":"Biological Insights into Muscular Strength: Genetic Findings in the UK Biobank","volume":"8","author":"Tikkanen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sarnowski, C., Chen, H., Biggs, M.L., Wassertheil-Smoller, S., Bressler, J., Irvin, M.R., Ryan, K.A., Karasik, D., Arnett, D.K., and Cupples, L.A. (2021). Identification of novel and rare variants associated with handgrip strength using whole genome sequence data from the NHLBI Trans-Omics in Precision Medicine (TOPMed) Program. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0253611"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1080\/03008207.2022.2104160","article-title":"Genome-wide association study of handgrip strength in the Northern Chinese adult twins","volume":"64","author":"Luo","year":"2023","journal-title":"Connect. Tissue Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41467-021-20918-w","article-title":"Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women","volume":"12","author":"Jones","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13459","DOI":"10.1111\/acel.13459","article-title":"A genome-wide association study of the frailty index highlights brain pathways in ageing","volume":"20","author":"Atkins","year":"2021","journal-title":"Aging Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1007\/s11357-023-00771-z","article-title":"A genome-wide association study of frailty identifies significant genetic correlation with neuropsychiatric, cardiovascular, and inflammation pathways","volume":"45","author":"Ye","year":"2023","journal-title":"Geroscience"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s42003-020-01256-x","article-title":"Genetic basis of falling risk susceptibility in the UK Biobank Study","volume":"3","author":"Trajanoska","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19493","DOI":"10.1038\/s41598-023-44566-w","article-title":"The genetics of falling susceptibility and identification of causal risk factors","volume":"13","author":"Smith","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1038\/s41598-022-07567-9","article-title":"Unveiling genetic variants for age-related sarcopenia by conducting a genome-wide association study on Korean cohorts","volume":"12","author":"Jin","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5969","DOI":"10.2147\/JIR.S338724","article-title":"A Genome-Wide Association Study Identifies Novel Risk Loci for Sarcopenia in a Taiwanese Population","volume":"14","author":"Wu","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"afad189","DOI":"10.1093\/ageing\/afad189","article-title":"The phenotypic and genotypic association of grip strength with frailty, physical performance and functional limitations over time in older adults","volume":"52","author":"Stringa","year":"2023","journal-title":"Age Ageing"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s40520-025-02997-7","article-title":"Sarcopenia-related traits and risk of falls in older adults: Results from meta-analysis of cohort studies and Mendelian randomization analyses","volume":"37","author":"Yang","year":"2025","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"glae051","DOI":"10.1093\/gerona\/glae051","article-title":"Metabolome-Wide Mendelian Randomization Assessing the Causal Relationship Between Blood Metabolites and Sarcopenia-Related Traits","volume":"79","author":"Chen","year":"2024","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.2147\/CIA.S424633","article-title":"A Bidirectional Mendelian Randomization Study of Sarcopenia-Related Traits and Knee Osteoarthritis","volume":"18","author":"Zhang","year":"2023","journal-title":"Clin. Interv. Aging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100776","DOI":"10.1016\/j.xcrm.2022.100776","article-title":"Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study","volume":"3","author":"Nethander","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s41043-024-00500-y","article-title":"Hand grip strength as a proposed new vital sign of health: A narrative review of evidences","volume":"43","author":"Vaishya","year":"2024","journal-title":"J. Health Popul. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101271","DOI":"10.1016\/j.mam.2024.101271","article-title":"Biomarkers of frailty","volume":"97","year":"2024","journal-title":"Mol. Asp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Boucham, M., Salhi, A., El Hajji, N., Gbenonsi, G.Y., Belyamani, L., and Khalis, M. (2024). Factors associated with frailty in older people: An umbrella review. BMC Geriatr., 24.","DOI":"10.1186\/s12877-024-05288-4"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/jcsm.13198","article-title":"Gene polymorphisms associated with heterogeneity and senescence characteristics of sarcopenia in chronic obstructive pulmonary disease","volume":"14","author":"Attaway","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pratt, J., Boreham, C., Ennis, S., Ryan, A.W., and De Vito, G. (2020). Genetic Associations with Aging Muscle: A Systematic Review. Cells, 9.","DOI":"10.3390\/cells9010012"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e1267","DOI":"10.1002\/mgg3.1267","article-title":"Whole-exome sequencing and genome-wide association studies identify novel sarcopenia risk genes in Han Chinese","volume":"8","author":"Ran","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Nedelcu, A.-D., Uzun, A.-B., Ciortea, V.-M., Irsay, L., Stanciu, L.-E., Iliescu, D.M., Popa, F.L., and Iliescu, M.-G. (2025). Genetic Patterns Related with the Development and Progression of Sarcopenia and Sarcopenic Obesity: A Systematic Review. Medicina, 61.","DOI":"10.3390\/medicina61050866"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"glae025","DOI":"10.1093\/gerona\/glae025","article-title":"Exome-Wide Sequencing Study Identified Genetic Variants Associated with Sarcopenic Obesity","volume":"79","author":"Xu","year":"2024","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Qiu, P., Chen, M., Lv, S., Xie, J., and Wu, J. (2023). The association between walking pace and hand grip strength with the risk of chronic obstructive pulmonary disease: A bidirectional Mendelian randomization study. BMC Pulm. Med., 23.","DOI":"10.1186\/s12890-023-02759-z"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yu, Z., He, J., Chen, Y., Zhou, Z., and Wang, L. (2024). Chronic obstructive pulmonary disease as a risk factor for sarcopenia: A systematic review and meta-analysis. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0300730"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"112953","DOI":"10.1016\/j.exger.2025.112953","article-title":"Causal relationships between sarcopenia, frailty, and health outcomes: A systematic review of Mendelian randomization studies","volume":"212","author":"Alekna","year":"2025","journal-title":"Exp. Gerontol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1357\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:41:47Z","timestamp":1787132507000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/8\/1357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["life16081357"],"URL":"https:\/\/doi.org\/10.3390\/life16081357","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]}}}