{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:06:39Z","timestamp":1777565199397,"version":"3.51.4"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T00:00:00Z","timestamp":1429574400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T00:00:00Z","timestamp":1429574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prion diseases are rare neurodegenerative conditions causing highly variable clinical syndromes, which often include prominent neuropsychiatric symptoms. We have recently carried out a clinical study of behavioural and psychiatric symptoms in a large prospective cohort of patients with prion disease in the United Kingdom, allowing us to operationalise specific behavioural\/psychiatric phenotypes as traits in human prion disease. Here, we report exploratory genome-wide association analysis on 170 of these patients and 5200 UK controls, looking for single-nucleotide polymorphisms (SNPs) associated with three behavioural\/psychiatric phenotypes in the context of prion disease. We also specifically examined a selection of candidate SNPs that have shown genome-wide association with psychiatric conditions in previously published studies, and the codon 129 polymorphism of the prion protein gene, which is known to modify various aspects of the phenotype of prion disease. No SNPs reached genome-wide significance, and there was no evidence of altered burden of known psychiatric risk alleles in relevant prion cases. SNPs showing suggestive evidence of association (<jats:italic>P<\/jats:italic>&lt;10<jats:sup>\u22125<\/jats:sup>) included several lying near genes previously implicated in association studies of other psychiatric and neurodegenerative diseases. These include<jats:italic>ANK3<\/jats:italic>,<jats:italic>SORL1<\/jats:italic>and a region of chromosome 6p containing several genes implicated in schizophrenia and bipolar disorder. We would encourage others to acquire phenotype data in independent cohorts of patients with prion disease as well as other neurodegenerative and neuropsychiatric conditions, to allow meta-analysis that may shed clearer light on the biological basis of these complex disease manifestations, and the diseases themselves.<\/jats:p>","DOI":"10.1038\/tp.2015.42","type":"journal-article","created":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T14:24:24Z","timestamp":1429626264000},"page":"e552-e552","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genome-wide association study of behavioural and psychiatric features in human prion disease"],"prefix":"10.1038","volume":"5","author":[{"given":"A G B","family":"Thompson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Uphill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Lowe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M-C","family":"Porter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Lukic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Carswell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Rudge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"MacKay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Collinge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Mead","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,4,21]]},"reference":[{"key":"BFtp201542_CR1","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1146\/annurev.neuro.24.1.519","volume":"24","author":"J Collinge","year":"2001","unstructured":"Collinge J . Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 2001; 24: 519\u2013550.","journal-title":"Annu Rev Neurosci"},{"key":"BFtp201542_CR2","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1176\/jnp.17.4.489","volume":"17","author":"CA Wall","year":"2005","unstructured":"Wall CA, Rummans TA, Aksamit AJ, Krahn LE, Pankratz VS . Psychiatric manifestations of Creutzfeldt-Jakob disease: a 25-year analysis. J Neuropsychiatry Clin Neurosci 2005; 17: 489\u2013495.","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"BFtp201542_CR3","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/S0140-6736(97)03148-6","volume":"350","author":"M Zeidler","year":"1997","unstructured":"Zeidler M, Johnstone EC, Bamber RWK, Dickens CM, Fisher CJ, Francis AF et al. New variant Crutzfeldt-Jakob disease: psychiatric features. Lancet 1997; 350: 908\u2013910.","journal-title":"Lancet"},{"key":"BFtp201542_CR4","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W","volume":"46","author":"P Parchi","year":"1999","unstructured":"Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O et al. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224\u2013233.","journal-title":"Ann Neurol"},{"key":"BFtp201542_CR5","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1093\/bmb\/66.1.241","volume":"66","author":"JD Wadsworth","year":"2003","unstructured":"Wadsworth JD, Hill AF, Beck JA, Collinge J . Molecular and clinical classification of human prion disease. Br Med Bull 2003; 66: 241\u2013254.","journal-title":"Br Med Bull"},{"key":"BFtp201542_CR6","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.1093\/brain\/awh249","volume":"127","author":"M Pocchiari","year":"2004","unstructured":"Pocchiari M, Puopolo M, Croes EA, Budka H, Gelpi E, Collins S et al. Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies. Brain 2004; 127: 2348\u20132359.","journal-title":"Brain"},{"key":"BFtp201542_CR7","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1176\/appi.ajp.2013.12111460","volume":"171","author":"A Thompson","year":"2014","unstructured":"Thompson A, Mackay A, Rudge P, Lukic A, Porter MC, Lowe J et al. Behavioral and psychiatric symptoms in prion disease. Am J Psychiatry 2014; 171: 265\u2013274.","journal-title":"Am J Psychiatry"},{"key":"BFtp201542_CR8","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/S1474-4422(09)70049-3","volume":"2009","author":"J Collinge","year":"2009","unstructured":"Collinge J, Gorham M, Hudson F, Kennedy A, Keogh G, Pal S et al. Safety and efficacy of quinacrine in human prion disease (PRION-1 study): a patient-preference trial. Lancet Neurol 2009; 2009: 334\u2013344.","journal-title":"Lancet Neurol"},{"key":"BFtp201542_CR9","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1093\/brain\/awt048","volume":"136","author":"AG Thompson","year":"2013","unstructured":"Thompson AG, Lowe J, Fox Z, Lukic A, Porter MC, Ford L et al. The Medical Research Council Prion Disease Rating Scale: a new outcome measure for prion disease therapeutic trials developed and validated using systematic observational studies. Brain 2013; 136: 1116\u20131127.","journal-title":"Brain"},{"key":"BFtp201542_CR10","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1093\/hmg\/ddr607","volume":"21","author":"S Mead","year":"2011","unstructured":"Mead S, Uphill J, Beck J, Poulter M, Campbell T, Lowe J et al. Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP. Hum Mol Genet 2011; 21: 1897\u20131906.","journal-title":"Hum Mol Genet"},{"key":"BFtp201542_CR11","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1038\/mp.2011.125","volume":"17","author":"P Hollingworth","year":"2011","unstructured":"Hollingworth P, Sweet R, Sims R, Harold D, Russo G, Abraham R et al. Genome-wide association study of Alzheimer's disease with psychotic symptoms. Mol Psychiatry 2011; 17: 1316\u20131327.","journal-title":"Mol Psychiatry"},{"key":"BFtp201542_CR12","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1093\/brain\/awp191","volume":"132","author":"I Zerr","year":"2009","unstructured":"Zerr I, Kallenberg K, Summers DM, Romero C, Taratuto A, Heinemann U et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain 2009; 132: 2659\u20132668.","journal-title":"Brain"},{"key":"BFtp201542_CR13","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/ana.21987","volume":"67","author":"CA Heath","year":"2010","unstructured":"Heath CA, Cooper SA, Murray K, Lowman A, Henry C, Macleod MA et al. Validation of diagnostic criteria for variant Creutzfeldt-Jakob disease. Ann Neurol 2010; 67: 761\u2013770.","journal-title":"Ann Neurol"},{"key":"BFtp201542_CR14","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1212\/WNL.0b013e3182364890","volume":"77","author":"S Mead","year":"2011","unstructured":"Mead S, Ranopa M, Gopalakrishnan GS, Thompson AGB, Rudge P, Wroe S et al. PRION-1 scales analysis supports use of functional outcome measures in prion disease. Neurology 2011; 77: 1674\u20131683.","journal-title":"Neurology"},{"key":"BFtp201542_CR15","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/nature08186","volume":"460","author":"H Stefansson","year":"2009","unstructured":"Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D et al. Common variants conferring risk of schizophrenia. Nature 2009; 460: 744\u2013U99.","journal-title":"Nature"},{"key":"BFtp201542_CR16","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1038\/ng.209","volume":"40","author":"MAR Ferreira","year":"2008","unstructured":"Ferreira MAR, O'Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008; 40: 1056\u20131058.","journal-title":"Nat Genet"},{"key":"BFtp201542_CR17","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.ajhg.2011.01.017","volume":"88","author":"S Cichon","year":"2011","unstructured":"Cichon S, Muhleisen TW, Degenhardt FA, Mattheisen M, Miro X, Strohmaier J et al. Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. Am J Hum Genet 2011; 88: 372\u2013381.","journal-title":"Am J Hum Genet"},{"key":"BFtp201542_CR18","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/ng.523","volume":"42","author":"FJ McMahon","year":"2010","unstructured":"McMahon FJ, Akula N, Schulze TG, Muglia P, Tozzi F, Detera-Wadleigh SD et al. Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1. Nat Genet 2010; 42: 128\u2013U52.","journal-title":"Nat Genet"},{"key":"BFtp201542_CR19","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/mp.2008.131","volume":"15","author":"P Muglia","year":"2010","unstructured":"Muglia P, Tozzi F, Galwey NW, Francks C, Upmanyu R, Kong XQ et al. Genome-wide association study of recurrent major depressive disorder in two European case-control cohorts. Mol Psychiatry 2010; 15: 589\u2013601.","journal-title":"Mol Psychiatry"},{"key":"BFtp201542_CR20","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.molmed.2007.11.005","volume":"14","author":"V Bennett","year":"2008","unstructured":"Bennett V, Healy J . Organizing the diseases fluid membrane bilayer: diseases linked to spectrin and ankyrin. Trends Mol Med 2008; 14: 28\u201336.","journal-title":"Trends Mol Med"},{"key":"BFtp201542_CR21","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1093\/hmg\/ddq471","volume":"20","author":"HJ Williams","year":"2011","unstructured":"Williams HJ, Craddock N, Russo G, Hamshere ML, Moskvina V, Dwyer S et al. Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-traditional diagnostic boundaries. Hum Mol Gen 2011; 20: 387\u2013391.","journal-title":"Hum Mol Gen"},{"key":"BFtp201542_CR22","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s00439-003-1075-5","volume":"114","author":"A Stenzel","year":"2004","unstructured":"Stenzel A, Lu T, Koch WA, Hampe J, Guenther SM, De la Vega FM et al. Patterns of linkage disequilibrium in the MHC region on human chromosome 6p. Hum Genet 2004; 114: 377\u2013385.","journal-title":"Hum Genet"},{"key":"BFtp201542_CR23","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1016\/S0140-6736(12)62129-1","volume":"381","author":"JW Smoller","year":"2013","unstructured":"Smoller JW, Craddock N, Kendler K, Lee PH, Neale BM, Nurnberger JI et al. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013; 381: 1371\u20131379.","journal-title":"Lancet"},{"key":"BFtp201542_CR24","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/nature08185","volume":"460","author":"SM Purcell","year":"2009","unstructured":"Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460: 748\u2013752.","journal-title":"Nature"},{"key":"BFtp201542_CR25","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/mp.2012.157","volume":"19","author":"S Steinberg","year":"2014","unstructured":"Steinberg S, de Jong S, Mattheisen M, Costas J, Demontis D, Jamain S et al. Common variant at 16p11.2 conferring risk of psychosis. Mol Psychiatry 2014; 19: 108\u2013114.","journal-title":"Mol Psychiatry"},{"key":"BFtp201542_CR26","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/ng.2805","volume":"45","author":"SH Lee","year":"2013","unstructured":"Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet 2013; 45: 984\u2013985.","journal-title":"Nat Genet"},{"key":"BFtp201542_CR27","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/sj.mp.4002106","volume":"13","author":"JE Chubb","year":"2008","unstructured":"Chubb JE, Bradshaw NJ, Soares DC, Porteous DJ, Millar JK . The DISC locus in psychiatric illness. Mol Psychiatry 2008; 13: 36\u201364.","journal-title":"Mol Psychiatry"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/tp201542.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/tp201542","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/tp201542.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T14:28:05Z","timestamp":1717856885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/tp201542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,21]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4]]}},"alternative-id":["BFtp201542"],"URL":"https:\/\/doi.org\/10.1038\/tp.2015.42","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,21]]},"assertion":[{"value":"22 March 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 February 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}