{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:17:45Z","timestamp":1792113465624,"version":"4.4.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"11","funder":[{"DOI":"10.13039\/100006492","name":"Intramural Research Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1ZIA-NS003154, Z01-AG000949-02, Z01-ES101986 and UK ADC NIA P30 AG072946"],"award-info":[{"award-number":["1ZIA-NS003154, Z01-AG000949-02, Z01-ES101986 and UK ADC NIA P30 AG072946"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Biobank","award":["33601"],"award-info":[{"award-number":["33601"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Parkinson\u2019s disease has a large heritable component and genome-wide association studies have identified over 90 variants with disease-associated common variants, providing deeper insights into the disease biology. However, there have not been large-scale rare variant analyses for Parkinson\u2019s disease.<\/jats:p>\n               <jats:p>To address this gap, we investigated the rare genetic component of Parkinson\u2019s disease at minor allele frequencies &amp;lt;1%, using whole genome and whole exome sequencing data from 7184 Parkinson\u2019s disease cases, 6701 proxy cases and 51 650 healthy controls from the Accelerating Medicines Partnership Parkinson's disease (AMP-PD) initiative, the National Institutes of Health, the UK Biobank and Genentech. We performed burden tests meta-analyses on small indels and single nucleotide protein-altering variants, prioritized based on their predicted functional impact.<\/jats:p>\n               <jats:p>Our work identified several genes reaching exome-wide significance. Two of these genes, GBA1 and LRRK2, have variants that have been previously implicated as risk factors for Parkinson\u2019s disease, with some variants in LRRK2 resulting in monogenic forms of the disease. We identify potential novel risk associations for variants in B3GNT3, AUNIP, ADH5, TUBA1B, OR1G1, CAPN10 and TREML1 but were unable to replicate the observed associations across independent datasets. Of these, B3GNT3 and TREML1 could provide new evidence for the role of neuroinflammation in Parkinson\u2019s disease. To date, this is the largest analysis of rare genetic variants in Parkinson\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awad214","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T18:25:47Z","timestamp":1687631147000},"page":"4622-4632","source":"Crossref","is-referenced-by-count":55,"title":["Large-scale rare variant burden testing in Parkinson's disease"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-6281","authenticated-orcid":false,"given":"Mary B","family":"Makarious","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology , London WC1N 3BG , UK"},{"name":"UCL Movement Disorders Centre, University College London , London WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Lake","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Pitz","sequence":"additional","affiliation":[{"name":"Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Ye Fu","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Department of Cell Biology and Neuroscience, Rutgers University , Piscataway, NJ 08854 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L","family":"Guidubaldi","sequence":"additional","affiliation":[{"name":"Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20814 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Warly","family":"Solsberg","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California San Francisco , San Francisco, CA 94158 , USA"},{"name":"Pharmaceutical Sciences and Pharmacogenomics, University of California San Francisco , San Francisco, CA 94143 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bandres-Ciga","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20814 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hampton L","family":"Leonard","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Data Tecnica International , Washington, DC 20812 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonggeol Jeffrey","family":"Kim","sequence":"additional","affiliation":[{"name":"Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London , London EC1M 6BQ , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2623-5997","authenticated-orcid":false,"given":"Kimberley J","family":"Billingsley","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20814 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis P","family":"Grenn","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar Alvarez","family":"Jerez","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20814 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea X","family":"Alvarado","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Data Tecnica International , Washington, DC 20812 , 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and Technology , Hong Kong SAR , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"UK Brain Expression Consortium (UKBEC),","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6623-0429","authenticated-orcid":false,"given":"Sonja W","family":"Scholz","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke , Bethesda, MD 20814 , USA"},{"name":"Department of Neurology, Johns Hopkins University Medical Center , Baltimore, MD 21287 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan J","family":"Traynor","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Department of Neurology, Johns Hopkins University Medical Center , Baltimore, MD 21287 , 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National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Data Tecnica International , Washington, DC 20812 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar","family":"Bhangale","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Genentech, Inc. , South San Francisco, CA 94080 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9358-8111","authenticated-orcid":false,"given":"Cornelis","family":"Blauwendraat","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health , Bethesda, MD 20814 , USA"},{"name":"Integrative Neurogenomics Unit, Laboratory of Neurogenetics, 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