{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:25:24Z","timestamp":1782271524116,"version":"3.54.5"},"reference-count":16,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T00:00:00Z","timestamp":1577404800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stat Methods Med Res"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p> Information on the age at onset distribution of the asymptomatic stage of a disease can be of paramount importance in early detection and timely management of that disease. However, accurately estimating this distribution is challenging, because the asymptomatic stage is difficult to recognize for the patient and is often detected as an incidental finding or in case of recommended screening; the age at onset is often interval-censored. In this paper, we propose a method for the estimation of the age at onset distribution of the asymptomatic stage of a genetic disease based on ascertained pedigree data that take into account the way the data are ascertained to overcome selection bias. Simulation studies show that the estimates seem to be asymptotically unbiased. Our work is motivated by the analysis of data on facioscapulohumeral muscular dystrophy, a genetic muscle disorder. In our application, carriers of the genetic causal variant are identified through genetic screening of the relatives of symptomatic carriers and their disease status is determined by a medical examination. The estimates reveal an early age at onset of the asymptomatic stage of facioscapulohumeral muscular dystrophy. <\/jats:p>","DOI":"10.1177\/0962280219893400","type":"journal-article","created":{"date-parts":[[2019,12,27]],"date-time":"2019-12-27T10:29:58Z","timestamp":1577442598000},"page":"2344-2359","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Estimating the age at onset distribution of the asymptomatic stage of a genetic disease based on pedigree data"],"prefix":"10.1177","volume":"29","author":[{"given":"Marianne A","family":"Jonker","sequence":"first","affiliation":[{"name":"Department for Health Evidence, Section Biostatistics, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Vart","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Section Biostatistics, Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Rodriguez Girondo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,12,27]]},"reference":[{"key":"bibr1-0962280219893400","doi-asserted-by":"crossref","unstructured":"Halk AB, Potjer TP, Kukutsch NA, et\u00a0al. Surveillance for familial melanoma: recommendations from a national centre of expertise. Br J Dermatol 2019;  181(3): 594\u2013596.","DOI":"10.1111\/bjd.17767"},{"key":"bibr2-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2016.07.008"},{"key":"bibr3-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1177\/0962280209105023"},{"key":"bibr4-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-0348-8621-5"},{"key":"bibr5-0962280219893400","doi-asserted-by":"crossref","unstructured":"Jewell NP, van der Laan M. Current status data: review, recent developments and open problems. In: Balakrishnan N and  Rao CR (eds) Handbook of statistics. Elsevier, Vol. 23. 2003, pp.625\u2013642.","DOI":"10.1016\/S0169-7161(03)23035-2"},{"key":"bibr6-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7373"},{"key":"bibr7-0962280219893400","doi-asserted-by":"crossref","unstructured":"Jonker MA, Rijken J, Hes FJ, et\u00a0al. Estimating the penetrance of pathogenic gene variants in families with missing pedigree information. Stat Method Med Res 2019;  28(10\u201311): 2924\u20132936.","DOI":"10.1177\/0962280218791338"},{"key":"bibr8-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20007"},{"key":"bibr9-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1086\/302808"},{"key":"bibr10-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13446"},{"key":"bibr11-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005915"},{"key":"bibr12-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20493"},{"key":"bibr13-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2004.00249.x"},{"key":"bibr14-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj014"},{"key":"bibr15-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2013.818001"},{"key":"bibr16-0962280219893400","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2712"}],"container-title":["Statistical Methods in Medical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0962280219893400","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0962280219893400","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0962280219893400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T21:32:05Z","timestamp":1740864725000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0962280219893400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,27]]},"references-count":16,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1177\/0962280219893400"],"URL":"https:\/\/doi.org\/10.1177\/0962280219893400","relation":{},"ISSN":["0962-2802","1477-0334"],"issn-type":[{"value":"0962-2802","type":"print"},{"value":"1477-0334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,27]]}}}