{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:27:11Z","timestamp":1791923231523,"version":"4.3.4"},"reference-count":76,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020M673247"],"award-info":[{"award-number":["2020M673247"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) and Lewy body dementia (LBD) have many common features, including clinical manifestations, neurochemistry, and pathology, but little is known about their shared brain proteins and genetic factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To identify susceptibility\u2010related brain proteins that are shared between PD and LBD patients, proteome\u2010wide association studies (PWASs) were conducted by integrating human brain protein quantitative trait loci (pQTLs) with large\u2010scale genome\u2010wide association studies (GWASs) of both diseases. Subsequently, pleiotropy\u2010informed conditional false discovery rate (pleioFDR) analysis was performed to identify common risk genetic loci between PD and LBD. Finally, the downregulation of these risk genes in different disease states was validated by differential gene expression analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PWASs identified 12 PD risk proteins and nine LBD risk proteins, among which\n                      <jats:italic>TMEM175<\/jats:italic>\n                      (\n                      <jats:italic>z<\/jats:italic>\n                      <jats:sub>PD<\/jats:sub>\n                      \u2009=\u2009\u22127.25,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>PD<\/jats:sub>\n                      \u2009=\u20094.12E\u201013;\n                      <jats:italic>z<\/jats:italic>\n                      <jats:sub>LBD<\/jats:sub>\n                      \u2009=\u2009\u22126.02,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>LBD<\/jats:sub>\n                      \u2009=\u20091.75E\u201009) and\n                      <jats:italic>DOC2A<\/jats:italic>\n                      (\n                      <jats:italic>z<\/jats:italic>\n                      <jats:sub>PD<\/jats:sub>\n                      \u2009=\u2009\u22124.13,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>PD<\/jats:sub>\n                      \u2009=\u20093.71E\u201005;\n                      <jats:italic>z<\/jats:italic>\n                      <jats:sub>LBD<\/jats:sub>\n                      \u2009=\u2009\u22123.91,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>LBD<\/jats:sub>\n                      \u2009=\u20099.08E\u201005) were shared. PleioFDR analysis revealed that five genetic risk loci mapped to eight genes associated with PD and LBD, including the proteome\u2010wide significant risk gene\n                      <jats:italic>TMEM175<\/jats:italic>\n                      (ConjFDR\u2009=\u20095.74E\u201003). Differential expression analysis verified that\n                      <jats:italic>TMEM175<\/jats:italic>\n                      was significantly downregulated in the midbrains of PD patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.19E\u201002), and further exploration revealed that\n                      <jats:italic>TMEM175<\/jats:italic>\n                      was also dramatically downregulated in the substantia nigra of PD patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.16E\u201002) and incidental Lewy body disease patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20097.52E\u201003). Moreover,\n                      <jats:italic>TMEM175<\/jats:italic>\n                      was significantly downregulated in induced pluripotent stem cell\u2010derived dopaminergic neurons from PD patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20094.60E\u201002).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Dysregulation of\n                      <jats:italic>TMEM175<\/jats:italic>\n                      may confer PD and LBD risk and may be partly responsible for their comorbidity. Our results revealed the common genetic risk factors between PD and LBD, which elucidated the shared genetic basis of these diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70370","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T05:46:05Z","timestamp":1744177565000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of Common Brain Protein and Genetic Loci Between Parkinson's Disease and Lewy Body Dementia"],"prefix":"10.1111","volume":"31","author":[{"given":"Tingting","family":"Jia","sequence":"first","affiliation":[{"name":"Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy West China Hospital of Sichuan University  Chengdu Sichuan China"},{"name":"Department of Gastroenterology and Hepatology and Sichuan University\u2010University of Oxford Huaxi Joint Centre for Gastrointestinal 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