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The causal and longitudinal relationships between homocysteine (Hcy), B vitamins, and sarcopenia remain unclear. This study integrated genetic evidence with clinical cohort data to investigate these associations using a two\u2010stage design. First, we performed a two\u2010sample Mendelian randomization (MR) analysis using summary data from large\u2010scale genome\u2010wide association studies (GWAS) of European ancestry. We examined the potential causal effects of Hcy, Vit B\n                    <jats:sub>6<\/jats:sub>\n                    , folate, and Vit B\n                    <jats:sub>12<\/jats:sub>\n                    on sarcopenia\u2010related phenotypes, including appendicular lean mass (ALM), grip strength, and walking pace, using the inverse\u2010variance weighted (IVW) method as the primary analysis. Second, to validate these genetic findings and examine their longitudinal relevance, we established an independent retrospective clinical cohort of 1322 individuals. Group\u2010based trajectory modeling identified distinct Hcy trajectory groups, and multivariable Cox regression with restricted cubic splines was used to assess longitudinal associations and dose\u2013response relationships with incident sarcopenia. The MR analysis showed that genetically predicted higher Hcy levels were causally associated with low grip strength (OR\u2009=\u20091.133, 95% CI: 1.016\u20131.263,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.025) and lower ALM (\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2009=\u2009\u22120.043, 95% CI: \u22120.069 \u2013 \u22120.016,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001). In the clinical cohort, individuals in the medium\u2010stable and high\u2010stable Hcy trajectory groups had a 1.965\u2010fold (95% CI: 1.027\u20133.759) and 2.832\u2010fold (95% CI: 1.608\u20134.987) higher risk of developing sarcopenia, respectively, compared to the low\u2010stable group. A continuous, incremental dose\u2013response relationship was observed between baseline Hcy levels and sarcopenia risk (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). No robust genetic evidence supported causal roles for B vitamins in sarcopenia. This study provides evidence that Hcy is associated with sarcopenia risk, suggesting that interventions targeting Hcy may help prevent or delay sarcopenia onset.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71556","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:38:49Z","timestamp":1771241929000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetically Predicted Homocysteine Levels and B Vitamins on Sarcopenia\u2010Related Traits: Insights From an Observational and Mendelian Randomization Analysis"],"prefix":"10.1002","volume":"14","author":[{"given":"Caizheng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Nursing Shanxi Technology and Business University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Health Management The First Hospital of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangying","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Hospital\u2010Acquired Infection Management The Second Hospital of Shanxi Medical University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Nursing, Shanxi Bethune Hospital Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Nursing, Shanxi Bethune Hospital Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital  Taiyuan 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