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However, the causality remains uncertain.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Using the Mendelian randomization (MR) approach, we assessed the causal effects of genetically proxied reduced low-density lipoprotein cholesterol (LDL-C) through inhibitions of hydroxy-methyl-glutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin\/kexin type 9 (PCSK9), and Niemann-Pick C1-like 1 (NPC1L1) on sarcopenia-related traits, including low hand grip strength, appendicular lean mass, and usual walking pace. A meta-analysis was conducted to combine the causal estimates from different consortiums.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Using LDL-C pooled data predominantly from UK Biobank, genetically proxied inhibition of HMGCR was associated with higher appendicular lean mass (beta\u2009=\u20090.087, <jats:italic>P<\/jats:italic>\u2009=\u20097.56\u2009\u00d7\u200910<jats:sup>\u2212\u20095<\/jats:sup>) and slower walking pace (OR\u2009=\u20090.918, <jats:italic>P<\/jats:italic>\u2009=\u20096.06\u2009\u00d7\u200910<jats:sup>\u2212\u20099<\/jats:sup>). In contrast, inhibition of PCSK9 may reduce appendicular lean mass (beta = -0.050, <jats:italic>P<\/jats:italic>\u2009=\u20091.40\u2009\u00d7\u200910<jats:sup>\u2212\u20093<\/jats:sup>), while inhibition of NPC1L1 showed no causal impact on sarcopenia-related traits. These results were validated using LDL-C data from Global Lipids Genetics Consortium, indicating that HMGCR inhibition may increase appendicular lean mass (beta\u2009=\u20090.066, <jats:italic>P<\/jats:italic>\u2009=\u20092.17\u2009\u00d7\u200910<jats:sup>\u2212\u20093<\/jats:sup>) and decelerate walking pace (OR\u2009=\u20090.932, <jats:italic>P<\/jats:italic>\u2009=\u20091.43\u2009\u00d7\u200910<jats:sup>\u2212\u20096<\/jats:sup>), whereas PCSK9 inhibition could decrease appendicular lean mass (beta = -0.048, <jats:italic>P<\/jats:italic>\u2009=\u20091.69\u2009\u00d7\u200910<jats:sup>\u2212\u20096<\/jats:sup>). Meta-analysis further supported the robustness of these causal associations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Genetically proxied HMGCR inhibition may increase muscle mass but compromise muscle function, PCSK9 inhibition could result in reduced muscle mass, while NPC1L1 inhibition is not associated with sarcopenia-related traits and this class of drugs may serve as viable alternatives to sarcopenia individuals or those at an elevated risk.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40246-024-00643-3","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T12:02:13Z","timestamp":1720008133000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of lipid-lowering drugs with risk of sarcopenia: a drug target mendelian randomization study and meta-analysis"],"prefix":"10.1186","volume":"18","author":[{"given":"Jiaxin","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyang","family":"Zang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peihong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"issue":"9","key":"643_CR1","first-page":"589","volume":"99","author":"LE Hoover","year":"2019","unstructured":"Hoover LE. 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