{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:14:05Z","timestamp":1791026045492,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360437"],"award-info":[{"award-number":["82360437"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272452"],"award-info":[{"award-number":["82272452"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The association between brain and sarcopenia has not been clarified. We aim to investigate the causal association between brain structure, function, gene expression and sarcopenia\u2010related traits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      All participants were Europeans. GWAS data of Brain Imaging Data Structure (BIDs) was from the UK Biobank. Gene expression in 13 brain regions was acquired from the GTEx Consortium. The sarcopenia\u2010related traits, including appendicular lean mass (ALM), whole body lean mass (WBLM), grip strength and sarcopenia diagnosed by the European Working Group on Sarcopenia in Older People (EWGSOP) or Foundation for the National Institutes of Health (FNIH), were from the IEU website. The inverse variance weighted (IVW), MR Egger, weighted median, weighted mode and Wald ratio methods were used for a two\u2010sample Mendelian randomization (MR) analysis between brain structures and sarcopenia\u2010related traits. The summary\u2010data\u2010based MR (SMR) was used to investigate brain genes causally influencing sarcopenia. We calculated the\n                      <jats:italic>F<\/jats:italic>\n                      \u2010value, odds ratio with 95% CI and\n                      <jats:italic>p<\/jats:italic>\n                      \u2010value. For the sensitivity analysis, the heterogeneity\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      statistic, Cochrane's\n                      <jats:italic>Q<\/jats:italic>\n                      test, Egger's intercept test, MR\u2010PRESSO and the leave\u2010one\u2010out sensitivity test were used. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein\u2013protein interaction (PPI), transcription factor interaction prediction and miRNA interaction prediction analysis were used to reveal potential signalling pathways and mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 3144 imaging phenotypes from 8428 participants in BIDs data. One hundred forty\u2010one BIDs were identified to causally influence ALM, 160 BIDs showed significant causal effect on the WBLM, and 86 BIDs showed significant causal effect on grip strength. There were 48 or 32 BIDs causally associated with sarcopenia diagnosed by the EWGSOP or FNIH criteria respectively. After FDR correction, there were 35 BIDs showing causal effect on the ALM, 28 BIDs showing causal effect on the WBLM and 7 BIDs showing causal effect on grip strength (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Twelve to forty\u2010eight genes in different brain regions showed causal effect on all the five sarcopenia\u2010related traits. MMP24\u2010AS1, HLA\u2010DRB6, HLA\u2010DQA2, DDX42, BAG6, NUSAP1, LINC00940, NME1\u2010NME2 and AS3MT in the amygdala region showed detrimental effect on all the five sarcopenia\u2010related traits, whereas HLA\u2010DRB1, HLA\u2010DQB1\u2010AS1 and C6ORF3 showed protective effect (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). The gene enrichment analysis indicated these screened genes was mainly enriched in immune\u2010related signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We discovered the causal effect of BIDs and brain gene expression on sarcopenia. The positive genes were mainly enriched in immune\u2010related signalling, suggesting an immune\u2010based cross\u2010organ regulation mechanism of brain\u2013muscle axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13647","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T07:35:38Z","timestamp":1731483338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic Influence of the Brain on Muscle Structure: A Mendelian Randomization Study of Sarcopenia"],"prefix":"10.1002","volume":"16","author":[{"given":"Ting","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zichao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Wang","sequence":"additional","affiliation":[{"name":"The School of Medicine Nankai University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyu","family":"Nan","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Orthopedic, The First Affiliated Hospital, Key Laboratory of High Incidence Disease Research in Xinjiang, Ministry of Education Xinjiang Medical University  Urumqi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zewu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Urology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihe","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e328358d59b"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15051193"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S456451"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ihj.2022.12.004"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afac220"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2020.04.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1367"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12020297"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-021-02581-4"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-58416-w"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43586-021-00092-5"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyg070"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz240"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac963"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-023-06770-x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.039"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.2005.036665"},{"key":"e_1_2_7_19_1","first-page":"810","article-title":"Brainwide Mendelian Randomization Study of Anxiety Disorders and Symptoms","author":"Zanoaga M. 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