{"id":4690,"date":"2021-01-04T18:41:36","date_gmt":"2021-01-04T23:41:36","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/analysis-of-dnm3-and-vamp4-as-genetic-modifiers-of-lrrk2-parkinsons-disease-2\/"},"modified":"2024-12-03T14:57:23","modified_gmt":"2024-12-03T19:57:23","slug":"analysis-of-dnm3-and-vamp4-as-genetic-modifiers-of-lrrk2-parkinsons-disease-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/analysis-of-dnm3-and-vamp4-as-genetic-modifiers-of-lrrk2-parkinsons-disease-2\/","title":{"rendered":"Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson\u2019s disease"},"content":{"rendered":"<h2>Abstract<\/h2>\n<div id=\"sec-1\" class=\"subsection\">\n<p id=\"p-3\"><strong>Objective<\/strong> To assess genetic modifiers of Parkinson\u2019s disease (PD) age at onset (AAO) penetrance in individuals carrying common and rare <em>LRRK2<\/em> risk alleles<\/p>\n<\/div>\n<div id=\"sec-2\" class=\"subsection\">\n<p id=\"p-4\"><strong>Methods<\/strong> We analysed reported genetic modifier <em>DNM3<\/em> rs2421947 in 724 <em>LRRK2<\/em> p.G2019S heterozygotes using linear regression of AAO. We meta-analysed our data with previously published data (n=754). <em>VAMP4<\/em> is in close proximity to <em>DNM3<\/em> and is associated with PD. We analysed the effect of the rs11578699 <em>VAMP4<\/em> variant on pG2019S penetrance in 786 <em>LRRK2<\/em> p.G2019S heterozygotes. We also evaluated the impact of <em>VAMP4<\/em> variants using AAO regression in 4882 patients with PD carrying a common <em>LRRK2<\/em> risk variant (rs10878226).<\/p>\n<\/div>\n<div id=\"sec-3\" class=\"subsection\">\n<p id=\"p-5\"><strong>Results<\/strong> There was no evidence for linkage disequilibrium between DNM3 rs2421947 and <em>VAMP4<\/em> rs11578699. Our linear regression AAO of 724 p.G2019S carriers showed no relationship between <em>DNM3<\/em> rs2421947 and AAO (beta = \u22121.19, p = 0.55, n =708). Meta-analysis with previously published data did not indicate a significant effect on AAO (beta = \u22122.21, p = 0.083, n = 1304), but there was significant heterogeneity in the analyses of new and previously published data. <em>VAMP4<\/em> rs11578699 was nominally associated with AAO in patients dichotomized by the common <em>LRRK2<\/em> risk variant rs10878226 (beta=1.68, se=0.81 p=0.037).<\/p>\n<\/div>\n<div id=\"sec-4\" class=\"subsection\">\n<p id=\"p-6\"><strong>Interpretation<\/strong> Analysis of <em>DNM3<\/em> in previously unpublished data does not show an interaction between <em>DNM3<\/em> and <em>LRRK2<\/em> G2019S for AAO, however the inter-study heterogeneity may indicate ethnic-specific effects of <em>DNM3<\/em> rs2421947. Analysis of sporadic PD patients stratified by the PD risk variant rs10878226 indicates a possible interaction between <em>LRRK2<\/em> and <em>VAMP4<\/em>.<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4690","ccna_publication","type-ccna_publication","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson\u2019s disease - CCNA - CCNV<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/analysis-of-dnm3-and-vamp4-as-genetic-modifiers-of-lrrk2-parkinsons-disease-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson\u2019s disease - 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