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Gamma frailty model for linkage analysis with application to interval-censored migraine data
Authors:Jonker M A  Bhulai S  Boomsma D I  Ligthart R S L  Posthuma D  Van der Vaart A W
Affiliation:Department of Mathematics, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1081 a, 1081 HV Amsterdam, The Netherlands. majonker@few.vu.nl
Abstract:For many diseases, it seems that the age at onset is geneticallyinfluenced. Therefore, the age-at-onset data are often collectedin order to map the disease gene(s). The ages are often (right)censored or truncated, and therefore, many standard techniquesfor linkage analysis cannot be used. In this paper, we presenta correlated frailty model for censored survival data of siblings.The model is used for testing heritability for the age at onsetand linkage between the loci and the gene(s) that influence(s)the survival time. The model is applied to interval-censoredmigraine twin data. Heritability (obtained from the frailtiesrather than actual onset times) was estimated as 0.42; thisvalue was highly significant. The highest lod score, a scoreof 1.9, was found at the end of chromosome 19.
Keywords:Additive gamma frailty model   Heritability   IBD sharing   Interval censoring   Likelihood ratio test   Linkage analysis   Migraine   Survival data
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