{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:24:50Z","timestamp":1783445090999,"version":"3.54.6"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":320,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015569","name":"Canadian Consortium on Neurodegeneration in Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["154301"],"award-info":[{"award-number":["154301"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fonds de recherche du Qu\u00e9bec\u2014Sant\u00e9"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Two recent studies suggested that the APOE \u03b54 haplotype was associated with increased \u03b1-synuclein pathology in cell and mouse models. Genetic variants in the SNCA region have strong association with Parkinson\u2019s disease (PD), dementia with Lewy bodies (DLB) and idiopathic REM sleep behaviour disorder (iRBD), while APOE is a genetic risk determinant for only DLB. To determine if genetic-level interactions between SNCA and APOE exists that can explain the protein-level association, we investigated the genotypic interaction of APOE and SNCA in cohorts of PD, DLB and iRBD. We analysed genome-wide association study (GWAS) data from 5229 PD patients and 5480 controls, 2610 DLB patients and 1920 controls, and 1055 iRBD patients and 3667 controls. We used logistic regression interaction models across all three cohorts independently between the (i) top GWAS signals of SNCA single nucleotide polymorphisms (SNPs) and APOE haplotypes and (ii) SNP\u00d7SNP and three-way SNP interaction across the entire coding region plus 200\u2005kb flanking each gene. No significant interactions were found to be associated with any of the synucleinopathies after correction for multiple testing. Our results do not support a role for genetic interactions between APOE and SNCA across PD, DLB and iRBD. Since the tested genetic variants affect the expression and function of these proteins, it is likely that any interactions between them do not affect the risk of PD, DLB and iRBD.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf455","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T12:26:00Z","timestamp":1763382360000},"source":"Crossref","is-referenced-by-count":1,"title":["Lack of epistatic interaction of\n                    <i>SNCA<\/i>\n                    with\n                    <i>APOE<\/i>\n                    in synucleinopathies"],"prefix":"10.1093","volume":"7","author":[{"given":"Prabhjyot","family":"Saini","sequence":"first","affiliation":[{"name":"Montreal Neurological Institute, McGill University , Montreal, Quebec , H3A 1A1","place":["Canada"]},{"name":"Department of Human Genetics, McGill University , Montreal, Quebec , H3A 1Y2","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Yu","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, McGill University , Montreal, Quebec , H3A 1A1","place":["Canada"]},{"name":"Department of Human Genetics, McGill University , Montreal, Quebec , H3A 1Y2","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad A","family":"Estiar","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute, McGill University , Montreal, Quebec , H3A 1A1","place":["Canada"]},{"name":"Department of Human Genetics, McGill University , Montreal, Quebec , H3A 1Y2","place":["Canada"]},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University , Cambridge, MA 02142 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