{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:55:09Z","timestamp":1792130109625,"version":"4.4.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Intramural Research Programs"},{"DOI":"10.13039\/100000002","name":"NIH","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","award":["Z01-AG000949-02"],"award-info":[{"award-number":["Z01-AG000949-02"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000971","name":"ALS Association","doi-asserted-by":"publisher","award":["17-SI-386"],"award-info":[{"award-number":["17-SI-386"]}],"id":[{"id":"10.13039\/100000971","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["827015"],"award-info":[{"award-number":["827015"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Intermediate CAG (polyQ) expansions in the gene ataxin-2 (ATXN2) are now recognized as a risk factor for amyotrophic lateral sclerosis. The threshold for increased risk is not yet firmly established, with reports ranging from 27 to 31 repeats.<\/jats:p>\n               <jats:p>We investigated the presence of ATXN2 polyQ expansions in 9268 DNA samples collected from people with amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with frontotemporal dementia, frontotemporal dementia alone, Lewy body dementia and age matched controls.<\/jats:p>\n               <jats:p>This analysis confirmed ATXN2 intermediate polyQ expansions of \u226531 as a risk factor for amyotrophic lateral sclerosis with an odds ratio of 6.31. Expansions were an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia (odds ratio 27.59) and a somewhat lesser risk for frontotemporal dementia alone (odds ratio 3.14). There was no increased risk for Lewy body dementia. In a subset of 1362 patients with amyotrophic lateral sclerosis with complete clinical data, we could not confirm previous reports of earlier onset of amyotrophic lateral sclerosis or shorter survival in 25 patients with expansions.<\/jats:p>\n               <jats:p>These new data confirm \u226531 polyQ repeats in ATXN2 increase the risk for amyotrophic lateral sclerosis, and also for the first time show an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia. The lack of a more aggressive phenotype in amyotrophic lateral sclerosis patients with expansions has implications for ongoing gene-silencing trials for amyotrophic lateral sclerosis.<\/jats:p>","DOI":"10.1093\/brain\/awac167","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T20:06:32Z","timestamp":1651781192000},"page":"2671-2676","source":"Crossref","is-referenced-by-count":61,"title":["<i>ATXN2<\/i> intermediate expansions in amyotrophic lateral sclerosis"],"prefix":"10.1093","volume":"145","author":[{"given":"Jonathan D","family":"Glass","sequence":"first","affiliation":[{"name":"Department of Neurology, Emory University School of Medicine , Atlanta, GA 30322 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramita","family":"Dewan","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Ding","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH , Bethesda, MD 20892 , USA"},{"name":"Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6985-0658","authenticated-orcid":false,"given":"J Raphael","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifton","family":"Dalgard","sequence":"additional","affiliation":[{"name":"Uniformed Services University of the Health Sciences , Bethesda, MD 20814 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela J","family":"Keagle","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Massachusetts Medical School , Worcester, MA 01605 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Shankaracharya","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Massachusetts Medical School , Worcester, MA 01605 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Garc\u00eda-Redondo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciaon Hospital 12 de Octubre , Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan J","family":"Traynor","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH , Bethesda, MD 20892 , USA"},{"name":"National Institute of Neurological Disorders and Stroke (NINDS), NIH , Bethesda, MD , USA"},{"name":"Therapeutic Development Branch, National Center for Advancing Translational Sciences (NCATS), NIH , Rockville, MD 20850 , USA"},{"name":"Department of Neurology, Johns Hopkins University , Baltimore, MD 21287 , USA"},{"name":"Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Chia","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E","family":"Landers","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Massachusetts Medical School , Worcester, MA 01605 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"2023020110261761200_awac167-B1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-3-319-71779-1_8","article-title":"Spinocerebellar ataxia type 2","volume":"1049","author":"Scoles","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"2023020110261761200_awac167-B2","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.neuron.2018.05.002","article-title":"Ataxin-2 is droppin\u2019 some knowledge","volume":"98","author":"Becker","year":"2018","journal-title":"Neuron. 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