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Mouse quantitative trait locus (QTL) studies demonstrate multiple modifiers of incubation time unlinked to <jats:italic>Prnp<\/jats:italic>, suggesting the existence of homologous human prion disease modifiers, but direct evidence of these has been lacking. We investigated the correlation of age at onset and death, expressed as a composite <jats:italic>Z<\/jats:italic> score, between parents and offspring in three large UK inherited prion disease kindreds. Our analysis suggests that overall heritability of the composite phenotype is 0.55 (95% CI 0.35\u20130.75). This measure may be an underestimate of the total genetic contribution to phenotypic heterogeneity as the analysis does not incorporate the effect of <jats:italic>PRNP<\/jats:italic>\u2010linked modifiers. Although the confidence intervals are wide, these data suggest a significant heritable component to phenotypic variability and support attempts to identify human prion disease modifier genes which would be important in understanding the epidemiology of variant Creutzfeldt\u2013Jakob disease (vCJD) in populations with significant exposure to bovine spongiform encephalopathy (BSE) prions. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.30844","type":"journal-article","created":{"date-parts":[[2008,8,26]],"date-time":"2008-08-26T13:22:25Z","timestamp":1219756945000},"page":"496-501","source":"Crossref","is-referenced-by-count":10,"title":["Age of onset and death in inherited prion disease are heritable"],"prefix":"10.1002","volume":"150B","author":[{"given":"T.E.F.","family":"Webb","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Whittaker","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":"311","published-online":{"date-parts":[[2008,8,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.45.1.37"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90360-3"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)05128-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.048660"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)93128-V"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/115.3.687"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68930-7"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0492-64"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1580"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.101130398"},{"key":"e_1_2_6_12_1","volume-title":"Essence of statistics","author":"Loftus GR","year":"1988"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.10.1823"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201544"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/324710"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl226"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/352340a0"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/115.3.675"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90134-Z"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1976.00500040036005"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6320"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)09468-3"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.040931"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl076"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308679101"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69835-8"}],"container-title":["American Journal of Medical Genetics Part B: Neuropsychiatric Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.b.30844","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.b.30844","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:17:44Z","timestamp":1697674664000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.b.30844"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,26]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,6,5]]}},"alternative-id":["10.1002\/ajmg.b.30844"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.b.30844","archive":["Portico"],"relation":{},"ISSN":["1552-4841","1552-485X"],"issn-type":[{"value":"1552-4841","type":"print"},{"value":"1552-485X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,26]]}}}