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Biostatistics Advance Access originally published online on August 19, 2008
Biostatistics 2009 10(1):187-200; doi:10.1093/biostatistics/kxn027
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Gamma frailty model for linkage analysis with application to interval-censored migraine data

M. A. Jonker* and S. Bhulai

Department of Mathematics, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1081 a, 1081 HV Amsterdam, The Netherlands majonker{at}few.vu.nl

D. I. Boomsma, R. S. L. Ligthart and D. Posthuma

Department of Biological Psychology, Vrije Universiteit, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands

A. W. Van Der Vaart

Department of Mathematics, Faculty of Sciences, Vrije Universiteit, De Boelelaan 1081 a, 1081 HV Amsterdam, The Netherlands

* To whom correspondence should be addressed.

For many diseases, it seems that the age at onset is genetically influenced. Therefore, the age-at-onset data are often collected in order to map the disease gene(s). The ages are often (right) censored or truncated, and therefore, many standard techniques for linkage analysis cannot be used. In this paper, we present a correlated frailty model for censored survival data of siblings. The model is used for testing heritability for the age at onset and linkage between the loci and the gene(s) that influence(s) the survival time. The model is applied to interval-censored migraine twin data. Heritability (obtained from the frailties rather than actual onset times) was estimated as 0.42; this value was highly significant. The highest lod score, a score of 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

Received April 20, 2007; revised January 11, 2008; revised April 10, 2008; revised July 21, 2008; accepted for publication July 22, 2008.


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