{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:28:58Z","timestamp":1793946538411,"version":"4.8.0"},"reference-count":33,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic toggle=\"yes\">SLC25A46<\/jats:italic>\n                      gene encodes a mitochondrial carrier protein previously implicated in neuropathy and optic atrophy. Biallelic variants in\n                      <jats:italic toggle=\"yes\">SLC25A46<\/jats:italic>\n                      have been described in patients with Parkinson's disease (PD) with optic atrophy, but the evidence supporting a role in PD remains limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To assess whether\n                      <jats:italic toggle=\"yes\">SLC25A46<\/jats:italic>\n                      variants contribute to PD, REM sleep behavior disorder (RBD), or dementia with Lewy bodies (DLB).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined common variants using four representative PD genome-wide association studies (GWAS) and an RBD GWAS and applied summary-data-based Mendelian randomization (SMR) to evaluate whether genetically regulated expression of\n                      <jats:italic toggle=\"yes\">SLC25A46<\/jats:italic>\n                      shows a causal association with the risk of PD or RBD. Rare variant analyses were conducted in four cohorts of European descent: Accelerating Medicines Partnership: Parkinson's Disease (AMP-PD) PD (3,051 PD, 3,667 controls), UK Biobank (3,267 PD, 14,939 proxy, 54,800 controls), RBD (1,376 RBD, 2,580 controls), and AMP-PD DLB (2,605 DLB, 1,894 controls). Optimal sequence kernel association test (SKAT-O) and meta-analysis were used to assess rare variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No associations were observed between\n                      <jats:italic toggle=\"yes\">SLC25A46<\/jats:italic>\n                      variants and PD, RBD, or DLB. SMR analyses revealed no evidence supporting a causal relationship between\n                      <jats:italic toggle=\"yes\">SLC25A46<\/jats:italic>\n                      expression and PD or RBD risk. Rare variant burden analyses did not identify significant associations after multiple-testing correction across cohorts or meta-analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">SLC25A46<\/jats:italic>\n                      variants showed no evidence of association, suggesting the gene does not play a major role in PD, RBD, or DLB risk.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1877718x261452773","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T08:27:30Z","timestamp":1786004850000},"page":"1524-1531","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lack of genetic evidence for a role of SLC25A46 in alpha-synucleinopathies"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8495-2310","authenticated-orcid":false,"given":"Han","family":"Yu","sequence":"first","affiliation":[{"name":"McGill University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9026-114X","authenticated-orcid":false,"given":"Sitki Cem","family":"Parlar","sequence":"additional","affiliation":[{"name":"McGill University"},{"name":"Department of Human Genetics, McGill University, Montr\u00e9al, QC, Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University, Montr\u00e9al, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3407-5716","authenticated-orcid":false,"given":"Konstantin","family":"Senkevich","sequence":"additional","affiliation":[{"name":"McGill University"},{"name":"Department of Human Genetics, McGill University, Montr\u00e9al, QC, 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