{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:50:19Z","timestamp":1790952619211,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Observational studies have demonstrated a strong bidirectional association between frailty and depression, but it remains unclear whether this association reflects causality. This study aimed to examine the bidirectional causal relationship between frailty and depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using genome\u2010wide association study summary data, two\u2010sample Mendelian randomization was performed to test for the potential bidirectional causality between frailty, as defined by both the frailty index and the frailty phenotype, and depression. Several frailty\u2010related traits were additionally investigated, including weaker hand grip strength, slower walking pace and physical inactivity. Findings were replicated using an independent depression data source and verified using multiple sensitivity analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetically predicted higher frailty index (odds ratio [OR], 1.86; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), higher frailty phenotype score (OR, 2.79; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), lower grip strength (OR, 1.23; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003), slower walking pace (OR, 1.55; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.027) and physical inactivity (OR, 1.44; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003) all were associated with a higher risk of depression. As for the reverse direction, genetic liability to depression showed consistent associations with a higher frailty index (beta, 0.167; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and a higher frailty phenotype score (beta, 0.067; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.001), but not with other frailty\u2010related traits that were investigated. The results were stable across sensitivity analyses and across depression datasets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings add novel evidence supporting the bidirectional causal association between frailty and depression. Improving balance and muscle strength and increasing physical activity may be beneficial in both depression and frailty.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13319","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T06:45:48Z","timestamp":1693982748000},"page":"2327-2334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Assessment of the bidirectional causal association between frailty and depression: A Mendelian randomization study"],"prefix":"10.1002","volume":"14","author":[{"given":"Jiahao","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Public Health and the Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"},{"name":"Vanderbit Genetics Institute Vanderbilt University Medical Center  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyao","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health Hangzhou Medical College  Hangzhou 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