{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:58:25Z","timestamp":1789664305682,"version":"4.0.1"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010029","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["202306352"],"award-info":[{"award-number":["202306352"]}],"id":[{"id":"10.13039\/501100010029","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mitochondrial dysfunction is increasingly recognized as a key factor in neurodegenerative diseases (NDDs), underscoring the therapeutic potential of targeting mitochondria\u2010related genes. This study aimed to identify novel biomarkers and drug targets for these diseases through a comprehensive analysis that integrated genome\u2010wide Mendelian randomization (MR) with genes associated with mitochondrial function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using existing publicly available genome\u2010wide association studies (GWAS) summary statistics and comprehensive data on 1136 mitochondria\u2010related genes, we initially identified a subset of genes related to mitochondrial function that exhibited significant associations with NDDs. We then conducted colocalization and summary\u2010data\u2010based Mendelian randomization (SMR) analyses using expression quantitative trait loci (eQTL) to validate the causal role of these candidate genes. Additionally, we assessed the druggability of the encoded proteins to prioritize potential therapeutic targets for further exploration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Genetically predicted levels of 10 genes were found to be significantly associated with the risk of NDDs. Elevated\n                      <jats:italic>DMPK<\/jats:italic>\n                      and\n                      <jats:italic>LACTB2<\/jats:italic>\n                      levels were associated with increased Alzheimer's disease risk. Higher expression of\n                      <jats:italic>NDUFAF2<\/jats:italic>\n                      ,\n                      <jats:italic>BCKDK<\/jats:italic>\n                      , and\n                      <jats:italic>MALSU1<\/jats:italic>\n                      , along with lower\n                      <jats:italic>TTC19<\/jats:italic>\n                      , raised Parkinson's disease risk. Higher\n                      <jats:italic>ACLY<\/jats:italic>\n                      levels were associated with both amyotrophic lateral sclerosis and multiple sclerosis (MS) risks, while decreased\n                      <jats:italic>MCL1<\/jats:italic>\n                      ,\n                      <jats:italic>TOP3A<\/jats:italic>\n                      , and\n                      <jats:italic>VWA8<\/jats:italic>\n                      levels raised MS risk. These genes primarily impact mitochondrial function and energy metabolism. Notably, several druggable protein targets identified are being explored for potential NDDs treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This data\u2010driven MR study demonstrated the causal role of mitochondrial dysfunction in NDDs. Additionally, this study identified candidate genes that could serve as potential pharmacological targets for the prevention and treatment of NDDs. \u00a9 2025 International Parkinson and Movement Disorder Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.30123","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T04:10:13Z","timestamp":1737519013000},"page":"693-703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Mitochondria\u2010Related Genome\u2010Wide Mendelian Randomization Identifies Putatively Causal Genes for Neurodegenerative Diseases"],"prefix":"10.1002","volume":"40","author":[{"given":"Zheyi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"},{"name":"Department of Medical Experimental Center, Qingdao Key Lab of Mitochondrial Medicine, 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Mitochondrial Medicine, Qilu Hospital (Qingdao) Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyuan","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"},{"name":"Department of Medical Experimental Center, Qingdao Key Lab of Mitochondrial Medicine, Qilu Hospital (Qingdao) Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8170-7993","authenticated-orcid":false,"given":"Guanzhao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Qilu Hospital, Cheeloo College of Medicine Shandong University  Jinan China"},{"name":"Department of Medical Experimental Center, Qingdao Key Lab of Mitochondrial Medicine, Qilu Hospital (Qingdao) Shandong University  Qingdao 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