{"id":4679,"date":"2020-12-22T20:31:36","date_gmt":"2020-12-23T01:31:36","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/"},"modified":"2024-12-03T14:57:21","modified_gmt":"2024-12-03T19:57:21","slug":"targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/","title":{"rendered":"Targeted sequencing of Parkinson&rsquo;s disease loci genes highlights SYT11, FGF20 and other associations"},"content":{"rendered":"<h2 id=\"219913655\" class=\"abstract-title\">Abstract<\/h2>\n<section class=\"abstract\">\n<p class=\"chapter-para\">Genome-wide association studies (GWAS) have identified numerous loci associated with Parkinson\u2019s disease. The specific genes and variants that drive the associations within the vast majority of these loci are unknown. We aimed to perform a comprehensive analysis of selected genes to determine the potential role of rare and common genetic variants within these loci. We fully sequenced 32 genes from 25 loci previously associated with Parkinson\u2019s disease in 2657 patients and 3647 controls from three cohorts. Capture was done using molecular inversion probes targeting the exons, exon-intron boundaries and untranslated regions (UTRs) of the genes of interest, followed by sequencing. Quality control was performed to include only high-quality variants. We examined the role of rare variants (minor allele frequency &lt; 0.01) using optimized sequence Kernel association tests. The association of common variants was estimated using regression models adjusted for age, sex and ethnicity as required in each cohort, followed by a meta-analysis. After Bonferroni correction, we identified a burden of rare variants in <em>SYT11<\/em>, <em>FGF20<\/em> and <em>GCH1<\/em> associated with Parkinson\u2019s disease. Nominal associations were identified in 21 additional genes. Previous reports suggested that the <em>SYT11<\/em> GWAS association is driven by variants in the nearby <em>GBA<\/em> gene. However, the association of <em>SYT11<\/em> was mainly driven by a rare 3\u2032 UTR variant (rs945006601) and was independent of <em>GBA<\/em> variants (<em>P\u2009<\/em>=<em>\u2009<\/em>5.23\u2009\u00d7\u200910<sup>\u22125<\/sup> after exclusion of all <em>GBA<\/em> variant carriers). The association of <em>FGF20<\/em> was driven by a rare 5\u2032 UTR variant (rs1034608171) located in the promoter region. The previously reported association of <em>GCH1<\/em> with Parkinson\u2019s disease is driven by rare non-synonymous variants, some of which are known to cause dopamine-responsive dystonia. We also identified two <em>LRRK2<\/em> variants, p.Arg793Met and p.Gln1353Lys, in 10 and eight controls, respectively, but not in patients. We identified common variants associated with Parkinson\u2019s disease in <em>MAPT<\/em>, <em>TMEM175<\/em>, <em>BST1<\/em>, <em>SNCA<\/em> and <em>GPNMB<\/em>, which are all in strong linkage disequilibrium with known GWAS hits in their respective loci. A common coding <em>PM20D1<\/em> variant, p.Ile149Val, was nominally associated with reduced risk of Parkinson\u2019s disease (odds ratio 0.73, 95% confidence interval 0.60\u20130.89, <em>P\u2009<\/em>=<em>\u2009<\/em>1.161\u2009\u00d7\u200910<sup>\u22123<\/sup>). This variant is not in linkage disequilibrium with the top GWAS hits within this locus and may represent a novel association. These results further demonstrate the importance of fine mapping of GWAS loci, and suggest that <em>SYT11<\/em>, <em>FGF20<\/em>, and potentially <em>PM20D1<\/em>, <em>BST1<\/em> and <em>GPNMB<\/em> should be considered for future studies as possible Parkinson\u2019s disease-related genes.<\/p>\n<\/section>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4679","ccna_publication","type-ccna_publication","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Targeted sequencing of Parkinson&#039;s disease loci genes highlights SYT11, FGF20 and other associations - 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\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Targeted sequencing of Parkinson&#039;s disease loci genes highlights SYT11, FGF20 and other associations - CCNA - CCNV\" \/>\n<meta property=\"og:description\" content=\"Abstract Genome-wide association studies (GWAS) have identified numerous loci associated ...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/\" \/>\n<meta property=\"og:site_name\" content=\"CCNA - CCNV\" \/>\n<meta property=\"article:modified_time\" content=\"2024-12-03T19:57:21+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/ccna-ccnv.ca\/wp-content\/uploads\/2025\/01\/CCNA.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1200\" \/>\n\t<meta property=\"og:image:height\" content=\"675\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Estimation du temps de lecture\" \/>\n\t<meta name=\"twitter:data1\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/ccna_publication\\\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\\\/\",\"url\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/ccna_publication\\\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\\\/\",\"name\":\"Targeted sequencing of Parkinson's disease loci genes highlights SYT11, FGF20 and other associations - CCNA - CCNV\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/#website\"},\"datePublished\":\"2020-12-23T01:31:36+00:00\",\"dateModified\":\"2024-12-03T19:57:21+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/ccna_publication\\\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\\\/#breadcrumb\"},\"inLanguage\":\"fr-CA\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/ccna_publication\\\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/ccna_publication\\\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Targeted sequencing of Parkinson&#8217;s disease loci genes highlights SYT11, FGF20 and other associations\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/#website\",\"url\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/\",\"name\":\"Canadian Consortium on Neurodegeneration in Aging\",\"description\":\"\",\"publisher\":{\"@id\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/#organization\"},\"alternateName\":\"CCNA - CCNV\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"fr-CA\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/#organization\",\"name\":\"Canadian Consortium on Neurodegeneration in Aging\",\"alternateName\":\"CCNA - CCNV\",\"url\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"fr-CA\",\"@id\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"https:\\\/\\\/ccna-ccnv.ca\\\/wp-content\\\/uploads\\\/2025\\\/01\\\/ccna-logo-on-white-background.jpg\",\"contentUrl\":\"https:\\\/\\\/ccna-ccnv.ca\\\/wp-content\\\/uploads\\\/2025\\\/01\\\/ccna-logo-on-white-background.jpg\",\"width\":696,\"height\":696,\"caption\":\"Canadian Consortium on Neurodegeneration in Aging\"},\"image\":{\"@id\":\"https:\\\/\\\/ccna-ccnv.ca\\\/fr\\\/#\\\/schema\\\/logo\\\/image\\\/\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Targeted sequencing of Parkinson's disease loci genes highlights SYT11, FGF20 and other associations - CCNA - CCNV","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/","og_locale":"fr_CA","og_type":"article","og_title":"Targeted sequencing of Parkinson's disease loci genes highlights SYT11, FGF20 and other associations - CCNA - CCNV","og_description":"Abstract Genome-wide association studies (GWAS) have identified numerous loci associated ...","og_url":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/","og_site_name":"CCNA - CCNV","article_modified_time":"2024-12-03T19:57:21+00:00","og_image":[{"width":1200,"height":675,"url":"https:\/\/ccna-ccnv.ca\/wp-content\/uploads\/2025\/01\/CCNA.jpg","type":"image\/jpeg"}],"twitter_card":"summary_large_image","twitter_misc":{"Estimation du temps de lecture":"2 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/","url":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/","name":"Targeted sequencing of Parkinson's disease loci genes highlights SYT11, FGF20 and other associations - CCNA - CCNV","isPartOf":{"@id":"https:\/\/ccna-ccnv.ca\/fr\/#website"},"datePublished":"2020-12-23T01:31:36+00:00","dateModified":"2024-12-03T19:57:21+00:00","breadcrumb":{"@id":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/#breadcrumb"},"inLanguage":"fr-CA","potentialAction":[{"@type":"ReadAction","target":["https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/targeted-sequencing-of-parkinsons-disease-loci-genes-highlights-syt11-fgf20-and-other-associations\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/ccna-ccnv.ca\/fr\/"},{"@type":"ListItem","position":2,"name":"Targeted sequencing of Parkinson&#8217;s disease loci genes highlights SYT11, FGF20 and other associations"}]},{"@type":"WebSite","@id":"https:\/\/ccna-ccnv.ca\/fr\/#website","url":"https:\/\/ccna-ccnv.ca\/fr\/","name":"Canadian Consortium on Neurodegeneration in Aging","description":"","publisher":{"@id":"https:\/\/ccna-ccnv.ca\/fr\/#organization"},"alternateName":"CCNA - CCNV","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/ccna-ccnv.ca\/fr\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"fr-CA"},{"@type":"Organization","@id":"https:\/\/ccna-ccnv.ca\/fr\/#organization","name":"Canadian Consortium on Neurodegeneration in Aging","alternateName":"CCNA - CCNV","url":"https:\/\/ccna-ccnv.ca\/fr\/","logo":{"@type":"ImageObject","inLanguage":"fr-CA","@id":"https:\/\/ccna-ccnv.ca\/fr\/#\/schema\/logo\/image\/","url":"https:\/\/ccna-ccnv.ca\/wp-content\/uploads\/2025\/01\/ccna-logo-on-white-background.jpg","contentUrl":"https:\/\/ccna-ccnv.ca\/wp-content\/uploads\/2025\/01\/ccna-logo-on-white-background.jpg","width":696,"height":696,"caption":"Canadian Consortium on Neurodegeneration in Aging"},"image":{"@id":"https:\/\/ccna-ccnv.ca\/fr\/#\/schema\/logo\/image\/"}}]}},"_links":{"self":[{"href":"https:\/\/ccna-ccnv.ca\/fr\/wp-json\/wp\/v2\/ccna_publication\/4679","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ccna-ccnv.ca\/fr\/wp-json\/wp\/v2\/ccna_publication"}],"about":[{"href":"https:\/\/ccna-ccnv.ca\/fr\/wp-json\/wp\/v2\/types\/ccna_publication"}],"author":[{"embeddable":true,"href":"https:\/\/ccna-ccnv.ca\/fr\/wp-json\/wp\/v2\/users\/19"}],"wp:attachment":[{"href":"https:\/\/ccna-ccnv.ca\/fr\/wp-json\/wp\/v2\/media?parent=4679"}],"wp:term":[{"taxonomy":"studies-relation","embeddable":true,"href":"https:\/\/ccna-ccnv.ca\/fr\/wp-json\/wp\/v2\/studies-relation?post=4679"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}