{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:07:19Z","timestamp":1792260439553,"version":"4.4.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000016","name":"Department of Health and Human Services","doi-asserted-by":"publisher","award":["1ZIA-NS003154"],"award-info":[{"award-number":["1ZIA-NS003154"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"Department of Health and Human Services","doi-asserted-by":"publisher","award":["Z01-AG000949-02"],"award-info":[{"award-number":["Z01-AG000949-02"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"Department of Health and Human Services","doi-asserted-by":"publisher","award":["Z01-ES101986"],"award-info":[{"award-number":["Z01-ES101986"]}],"id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010785","name":"Canada First Research Excellence Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19-AG03365"],"award-info":[{"award-number":["U19-AG03365"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 NS38377"],"award-info":[{"award-number":["P50 NS38377"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50-AG005146"],"award-info":[{"award-number":["P50-AG005146"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease is a genetically complex disorder. Multiple genes have been shown to contribute to the risk of Parkinson\u2019s disease, and currently 90 independent risk variants have been identified by genome-wide association studies. Thus far, a number of genes (including SNCA, LRRK2, and GBA) have been shown to contain variability across a spectrum of frequency and effect, from rare, highly penetrant variants to common risk alleles with small effect sizes. Variants in GBA, encoding the enzyme glucocerebrosidase, are associated with Lewy body diseases such as Parkinson\u2019s disease and Lewy body dementia. These variants, which reduce or abolish enzymatic activity, confer a spectrum of disease risk, from 1.4- to &amp;gt;10-fold. An outstanding question in the field is what other genetic factors that influence GBA-associated risk for disease, and whether these overlap with known Parkinson\u2019s disease risk variants. Using multiple, large case-control datasets, totalling 217 165 individuals (22 757 Parkinson\u2019s disease cases, 13 431 Parkinson\u2019s disease proxy cases, 622 Lewy body dementia cases and 180 355 controls), we identified 1691 Parkinson\u2019s disease cases, 81 Lewy body dementia cases, 711 proxy cases and 7624 controls with a GBA variant (p.E326K, p.T369M or p.N370S). We performed a genome-wide association study and analysed the most recent Parkinson\u2019s disease-associated genetic risk score to detect genetic influences on GBA risk and age at onset. We attempted to replicate our findings in two independent datasets, including the personal genetics company 23andMe, Inc. and whole-genome sequencing data. Our analysis showed that the overall Parkinson\u2019s disease genetic risk score modifies risk for disease and decreases age at onset in carriers of GBA variants. Notably, this effect was consistent across all tested GBA risk variants. Dissecting this signal demonstrated that variants in close proximity to SNCA and CTSB (encoding cathepsin B) are the most significant contributors. Risk variants in the CTSB locus were identified to decrease mRNA expression of CTSB. Additional analyses suggest a possible genetic interaction between GBA and CTSB and GBA p.N370S induced pluripotent cell-derived neurons were shown to have decreased cathepsin B expression compared to controls. These data provide a genetic basis for modification of GBA-associated Parkinson\u2019s disease risk and age at onset, although the total contribution of common genetics variants is not large. We further demonstrate that common variability at genes implicated in lysosomal function exerts the largest effect on GBA associated risk for disease. Further, these results have implications for selection of GBA carriers for therapeutic interventions.<\/jats:p>","DOI":"10.1093\/brain\/awz350","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T15:11:53Z","timestamp":1571843513000},"page":"234-248","source":"Crossref","is-referenced-by-count":238,"title":["Genetic modifiers of risk and age at onset in GBA associated Parkinson\u2019s disease and Lewy body dementia"],"prefix":"10.1093","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9358-8111","authenticated-orcid":false,"given":"Cornelis","family":"Blauwendraat","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xylena","family":"Reed","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6554-1666","authenticated-orcid":false,"given":"Lynne","family":"Krohn","sequence":"first","affiliation":[{"name":"Department of Human Genetics, McGill University, Montreal, Quebec, Canada"},{"name":"Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Heilbron","sequence":"first","affiliation":[{"name":"23andMe, Inc., Mountain View, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bandres-Ciga","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5835-669X","authenticated-orcid":false,"given":"Manuela","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Raphael","family":"Gibbs","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dena G","family":"Hernandez","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindran","family":"Kumaran","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Langston","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Bonet-Ponce","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy N","family":"Alcalay","sequence":"first","affiliation":[{"name":"Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA"},{"name":"Taub Institute for Research on Alzheimer\u2019s Disease and the Aging Brain, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Hassin-Baer","sequence":"first","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"},{"name":"Department of Neurology, Sheba Medical Center, Tel Hashomer, Israel"},{"name":"Movement Disorders Institute, Sheba Medical Center, Tel Hashomer, Israel"},{"name":"The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lior","family":"Greenbaum","sequence":"first","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"},{"name":"The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel"},{"name":"The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8982-7885","authenticated-orcid":false,"given":"Hirotaka","family":"Iwaki","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hampton L","family":"Leonard","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis P","family":"Grenn","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A","family":"Ruskey","sequence":"first","affiliation":[{"name":"Department of Human Genetics, McGill University, Montreal, Quebec, Canada"},{"name":"Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marya","family":"Sabir","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ahmed","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary B","family":"Makarious","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse","family":"Pihlstr\u00f8m","sequence":"first","affiliation":[{"name":"Department of Neurology, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Toft","sequence":"first","affiliation":[{"name":"Department of Neurology, Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacobus J","family":"van Hilten","sequence":"first","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Marinus","sequence":"first","affiliation":[{"name":"Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Schulte","sequence":"first","affiliation":[{"name":"Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Brockmann","sequence":"first","affiliation":[{"name":"Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Sharma","sequence":"first","affiliation":[{"name":"Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Siitonen","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland"},{"name":"Department of Neurology and Medical Research Center, Oulu University Hospital, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Majamaa","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland"},{"name":"Department of Neurology and Medical Research Center, Oulu University Hospital, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Eerola-Rautio","sequence":"first","affiliation":[{"name":"Department of Neurology, Helsinki University Hospital, and Molecular Neurology, Research Programs Unit, Biomedicum, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pentti J","family":"Tienari","sequence":"first","affiliation":[{"name":"Department of Neurology, Helsinki University Hospital, and Molecular Neurology, Research Programs Unit, Biomedicum, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The 23andMe Research Team","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Pantelyat","sequence":"first","affiliation":[{"name":"Neuroregeneration and Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University Medical Center, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argye E","family":"Hillis","sequence":"first","affiliation":[{"name":"Neuroregeneration and Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University Medical Center, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-0893","authenticated-orcid":false,"given":"Ted M","family":"Dawson","sequence":"first","affiliation":[{"name":"Neuroregeneration and Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University Medical Center, Baltimore, MD, USA"},{"name":"Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liana S","family":"Rosenthal","sequence":"first","affiliation":[{"name":"Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn S","family":"Albert","sequence":"first","affiliation":[{"name":"Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M","family":"Resnick","sequence":"first","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Ferrucci","sequence":"first","affiliation":[{"name":"Longitudinal Studies Section, National Institute on Aging, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M","family":"Morris","sequence":"first","affiliation":[{"name":"Newcastle Brain Tissue Resource, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Pletnikova","sequence":"first","affiliation":[{"name":"Department of Pathology (Neuropathology, Johns Hopkins University Medical Center, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Troncoso","sequence":"first","affiliation":[{"name":"Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA"},{"name":"Department of Pathology (Neuropathology, Johns Hopkins University Medical Center, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Grosset","sequence":"first","affiliation":[{"name":"Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Lesage","sequence":"first","affiliation":[{"name":"Inserm U1127, Sorbonne Universit\u00e9s, UPMC Univ Paris 06 UMR S1127, Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, ICM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Corvol","sequence":"first","affiliation":[{"name":"Inserm U1127, Sorbonne Universit\u00e9s, UPMC Univ Paris 06 UMR S1127, Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, ICM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Brice","sequence":"first","affiliation":[{"name":"Inserm U1127, Sorbonne Universit\u00e9s, UPMC Univ Paris 06 UMR S1127, Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, ICM, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair J","family":"Noyce","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK"},{"name":"Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliezer","family":"Masliah","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Wood","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hardy","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Diseases, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Shulman","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Jankovic","sequence":"first","affiliation":[{"name":"Department of Neurology, Baylor College of Medicine, Houston, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M","family":"Shulman","sequence":"first","affiliation":[{"name":"Department of Neurology, Baylor College of Medicine, Houston, USA"},{"name":"Departments of Molecular and Human Genetics and Neuroscience, Baylor College of Medicine, Houston, USA"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children\u2019s Hospital, Houston, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Heutink","sequence":"first","affiliation":[{"name":"Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gasser","sequence":"first","affiliation":[{"name":"Hertie Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cannon","sequence":"first","affiliation":[{"name":"23andMe, Inc., Mountain View, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja W","family":"Scholz","sequence":"first","affiliation":[{"name":"Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA"},{"name":"Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huw","family":"Morris","sequence":"first","affiliation":[{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R","family":"Cookson","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike A","family":"Nalls","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"},{"name":"Data Tecnica International, Glen Echo, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-234X","authenticated-orcid":false,"given":"Ziv","family":"Gan-Or","sequence":"first","affiliation":[{"name":"Department of Human Genetics, McGill University, Montreal, Quebec, Canada"},{"name":"Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada"},{"name":"Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B","family":"Singleton","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,22]]},"reference":[{"key":"2020030305294656900_awz350-B1","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1093\/bioinformatics\/btx299","article-title":"FlashPCA2: principal component analysis of Biobank-scale genotype datasets","volume":"33","author":"Abraham","year":"2017","journal-title":"Bioinformatics"},{"key":"2020030305294656900_awz350-B2","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1093\/brain\/awv179","article-title":"Glucocerebrosidase activity in Parkinson's disease with and without GBA mutations","volume":"138","author":"Alcalay","year":"2015","journal-title":"Brain"},{"key":"2020030305294656900_awz350-B3","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1212\/WNL.0b013e318245f476","article-title":"Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers","volume":"78","author":"Anheim","year":"2012","journal-title":"Neurology"},{"key":"2020030305294656900_awz350-B4","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1002\/mds.103","article-title":"Coding variation in GBA explains the majority of the SYT11-GBA Parkinson's disease GWAS locus","volume":"33","author":"Blauwendraat","year":"2018","journal-title":"Mov Disord"},{"key":"2020030305294656900_awz350-B5","doi-asserted-by":"crossref","first-page":"247.e9","DOI":"10.1016\/j.neurobiolaging.2017.05.009","article-title":"NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases","volume":"57","author":"Blauwendraat","year":"2017","journal-title":"Neurobiol Aging"},{"key":"2020030305294656900_awz350-B6","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/mds.27659","article-title":"Parkinson's disease age at onset genome-wide association study: Defining heritability, genetic loci, and alpha-synuclein mechanisms","volume":"34","author":"Blauwendraat","year":"2019","journal-title":"Mov Disord"},{"key":"2020030305294656900_awz350-B7","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1001\/jamaneurol.2018.1885","article-title":"Frequency of Loss of function variants in LRRK2 in Parkinson disease","volume":"75","author":"Blauwendraat","year":"2018","journal-title":"JAMA Neurol"},{"key":"2020030305294656900_awz350-B117","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.mcn.2013.07.007","article-title":"A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells","volume":"56","author":"Burkhardt","year":"2013","journal-title":"Mol Cell Neurosci"},{"key":"2020030305294656900_awz350-B8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"2020030305294656900_awz350-B9","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","article-title":"The UK Biobank resource with deep phenotyping and genomic data","volume":"562","author":"Bycroft","year":"2018","journal-title":"Nature"},{"key":"2020030305294656900_awz350-B10","doi-asserted-by":"crossref","first-page":"7721","DOI":"10.1073\/pnas.83.20.7721","article-title":"Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs","volume":"83","author":"Chan","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"14","key":"2020030305294656900_awz350-B11","article-title":"27-Hydroxycholesterol contributes to lysosomal membrane permeabilization-mediated pyroptosis in co-cultured SH-SY5Y cells and C6 cells","volume":"12","author":"Chen","year":"2019","journal-title":"Front Mol Neurosci"},{"key":"2020030305294656900_awz350-B12","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The genotype-tissue expression (GTEx) project","volume":"45","author":"Consortium","year":"2013","journal-title":"Nat Genet"},{"key":"2020030305294656900_awz350-B13","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1007\/s00415-015-7868-3","article-title":"The Alzheimer disease BIN1 locus as a modifier of GBA-associated Parkinson disease","volume":"262","author":"Gan-Or","year":"2015","journal-title":"J Neurol"},{"key":"2020030305294656900_awz350-B14","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1212\/WNL.0000000000001315","article-title":"Differential effects of severe vs mild GBA mutations on Parkinson disease","volume":"84","author":"Gan-Or","year":"2015","journal-title":"Neurology"},{"key":"2020030305294656900_awz350-B15","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1080\/15548627.2015.1067364","article-title":"Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease","volume":"11","author":"Gan-Or","year":"2015","journal-title":"Autophagy"},{"key":"2020030305294656900_awz350-B16","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1212\/01.wnl.0000304039.11891.29","article-title":"Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset","volume":"70","author":"Gan-Or","year":"2008","journal-title":"Neurology"},{"key":"2020030305294656900_awz350-B17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/s11910-018-0860-4","article-title":"GBA-associated Parkinson's disease and other synucleinopathies","volume":"18","author":"Gan-Or","year":"2018","journal-title":"Curr Neurol Neurosci Rep"},{"key":"2020030305294656900_awz350-B18","doi-asserted-by":"crossref","first-page":"e1000952","DOI":"10.1371\/journal.pgen.1000952","article-title":"Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain","volume":"6","author":"Gibbs","year":"2010","journal-title":"PLoS Genet"},{"key":"2020030305294656900_awz350-B19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S1474-4422(17)30400-3","article-title":"Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study","volume":"17","author":"Guerreiro","year":"2018","journal-title":"Lancet Neurol"},{"key":"2020030305294656900_awz350-B20","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/nmeth.4407","article-title":"Massively parallel single-nucleus RNA-seq with DroNc-seq","volume":"14","author":"Habib","year":"2017","journal-title":"Nat Methods"},{"key":"2020030305294656900_awz350-B21","doi-asserted-by":"crossref","DOI":"10.1093\/hmg\/ddz136","article-title":"Functionalization of the TMEM175 p.M393T variant as a risk factor for Parkinson disease","author":"Jinn","year":"2019","journal-title":"Hum Mol Genet"},{"key":"2020030305294656900_awz350-B22","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1073\/pnas.1616332114","article-title":"TMEM175 deficiency impairs lysosomal and mitochondrial function and increases \u03b1-synuclein aggregation","volume":"114","author":"Jinn","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020030305294656900_awz350-B23","doi-asserted-by":"crossref","first-page":"e564","DOI":"10.1002\/mgg3.564","article-title":"Evaluation of the detection of GBA missense mutations and other variants using the Oxford Nanopore MinION","volume":"7","author":"Leija-Salazar","year":"2019","journal-title":"Mol Genet Genomic Med"},{"key":"2020030305294656900_awz350-B24","author":"Leonard","year":"2018"},{"key":"2020030305294656900_awz350-B25","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/hmg\/ddq454","article-title":"Large-scale screening of the Gaucher's disease-related glucocerebrosidase gene in Europeans with Parkinson's disease","volume":"20","author":"Lesage","year":"2011","journal-title":"Hum Mol Genet"},{"key":"2020030305294656900_awz350-B26","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/s41467-019-08912-9","article-title":"Prioritizing Parkinson's disease genes using population-scale transcriptomic data","volume":"10","author":"Li","year":"2019","journal-title":"Nat Commun"},{"key":"2020030305294656900_awz350-B27","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/s41588-019-0404-0","article-title":"Abundant associations with gene expression complicate GWAS follow-up","volume":"51","author":"Liu","year":"2019","journal-title":"Nat Genet"},{"key":"2020030305294656900_awz350-B28","doi-asserted-by":"crossref","first-page":"83907","DOI":"10.18632\/oncotarget.13438","article-title":"Ceramide activates lysosomal cathepsin B and cathepsin D to attenuate autophagy and induces ER stress to suppress myeloid-derived suppressor cells","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"key":"2020030305294656900_awz350-B29","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1136\/jnnp-2017-317348","article-title":"Features of -associated Parkinson's disease at presentation in the UK study","volume":"89","author":"Malek","year":"2018","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2020030305294656900_awz350-B30","doi-asserted-by":"crossref","first-page":"9322","DOI":"10.1073\/pnas.1500937112","article-title":"Cysteine cathepsins are essential in lysosomal degradation of \u03b1-synuclein","volume":"112","author":"McGlinchey","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020030305294656900_awz350-B31","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3233\/JAD-2006-9S347","article-title":"Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop","volume":"9","author":"McKeith","year":"2006","journal-title":"J Alzheimers Dis"},{"key":"2020030305294656900_awz350-B32","author":"Nalls","year":"2018"},{"key":"2020030305294656900_awz350-B33","doi-asserted-by":"crossref","first-page":"1605.e7","DOI":"10.1016\/j.neurobiolaging.2014.07.028","article-title":"NeuroX, a fast and efficient genotyping platform for investigation of neurodegenerative diseases","volume":"36","author":"Nalls","year":"2015","journal-title":"Neurobiol Aging"},{"key":"2020030305294656900_awz350-B34","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1002\/mds.26192","article-title":"Genetic risk and age in Parkinson's disease: continuum not stratum","volume":"30","author":"Nalls","year":"2015","journal-title":"Mov Disord"},{"key":"2020030305294656900_awz350-B35","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/S1474-4422(15)00178-7","article-title":"Diagnosis of Parkinson's disease on the basis of clinical and genetic classification: a population-based modelling study","volume":"14","author":"Nalls","year":"2015","journal-title":"Lancet Neurol"},{"key":"2020030305294656900_awz350-B36","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/ana.25274","article-title":"A comprehensive analysis of SNCA -related genetic risk in sporadic Parkinson disease","volume":"84","author":"Pihlstr\u00f8m","year":"2018","journal-title":"Ann Neurol"},{"key":"2020030305294656900_awz350-B37","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1093\/bioinformatics\/btq419","article-title":"LocusZoom: regional visualization of genome-wide association scan results","volume":"26","author":"Pruim","year":"2010","journal-title":"Bioinformatics"},{"key":"2020030305294656900_awz350-B38","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1038\/s41467-018-04558-1","article-title":"Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood","volume":"9","author":"Qi","year":"2018","journal-title":"Nat Commun"},{"key":"2020030305294656900_awz350-B39","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/gim.2012.107","article-title":"Age-specific Parkinson disease risk in GBA mutation carriers: information for genetic counseling","volume":"15","author":"Rana","year":"2013","journal-title":"Genet Med"},{"key":"2020030305294656900_awz350-B40","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0014-5793(85)81136-4","article-title":"Amino acid sequence of human liver cathepsin B","volume":"181","author":"Ritonja","year":"1985","journal-title":"FEBS Lett"},{"key":"2020030305294656900_awz350-B41","doi-asserted-by":"crossref","first-page":"e1007329","DOI":"10.1371\/journal.pgen.1007329","article-title":"Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population","volume":"14","author":"Rivas","year":"2018","journal-title":"PLoS Genet"},{"key":"2020030305294656900_awz350-B42","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1093\/brain\/awx285","article-title":"Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease","volume":"140","author":"Robak","year":"2017","journal-title":"Brain"},{"key":"2020030305294656900_awz350-B43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: an open-source package for R and S to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinform"},{"key":"2020030305294656900_awz350-B44","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ejmg.2018.05.005","article-title":"Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease","volume":"62","author":"Ruskey","year":"2019","journal-title":"Eur J Med Genet"},{"key":"2020030305294656900_awz350-B45","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","article-title":"Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease","volume":"361","author":"Sidransky","year":"2009","journal-title":"N Engl J Med"},{"key":"2020030305294656900_awz350-B46","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nature17939","article-title":"Parkinson-associated risk variant in distal enhancer of \u03b1-synuclein modulates target gene expression","volume":"533","author":"Soldner","year":"2016","journal-title":"Nature"},{"key":"2020030305294656900_awz350-B47","doi-asserted-by":"crossref","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med"},{"key":"2020030305294656900_awz350-B48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i03","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer","year":"2010","journal-title":"J Stat Softw"},{"key":"2020030305294656900_awz350-B49","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2020030305294656900_awz350-B50","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","article-title":"METAL: fast and efficient meta-analysis of genomewide association scans","volume":"26","author":"Willer","year":"2010","journal-title":"Bioinformatics"},{"key":"2020030305294656900_awz350-B51","first-page":"179","volume-title":"Parkinson's disease: Risk estimates and genotype-phenotype correlations. Parkinsonism Relat Disord","author":"Yahalom","year":"2019"},{"key":"2020030305294656900_awz350-B52","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ng.2213","article-title":"Genetic Investigation of ATC, Replication DIG, et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits","volume":"44","author":"Yang","year":"2012","journal-title":"Nat Genet"},{"key":"2020030305294656900_awz350-B53","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: a tool for genome-wide complex trait analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am J Hum Genet"},{"key":"2020030305294656900_awz350-B54","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1002\/mds.27631","article-title":"Emerging links between pediatric lysosomal storage diseases and adult parkinsonism","volume":"34","author":"Ysselstein","year":"2019","journal-title":"Mov Disord"},{"key":"2020030305294656900_awz350-B55","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1093\/bioinformatics\/btw079","article-title":"RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data","volume":"32","author":"Zhan","year":"2016","journal-title":"Bioinformatics"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/143\/1\/234\/32757155\/awz350.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/143\/1\/234\/32757155\/awz350.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T05:30:07Z","timestamp":1583213407000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/143\/1\/234\/5637818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,22]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,11,22]]},"published-print":{"date-parts":[[2020,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awz350","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/738351","asserted-by":"object"}]},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,1]]},"published":{"date-parts":[[2019,11,22]]}}}