title: Incorporation of the time aspect into the liability-threshold model for case-control-family data.
abstract: Familial aggregation and the role of genetic and environmental factors can be investigated through family studies analysed using the liability-threshold model. The liability-threshold model ignores the timing of events including the age of disease onset and right censoring, which can lead to estimates that are difficult to interpret and are potentially biased. We incorporate the time aspect into the liability-threshold model for case-control-family data following the same approach that has been applied in the twin setting. Thus, the data are considered as arising from a competing risks setting and inverse probability of censoring weights are used to adjust for right censoring. In the case-control-family setting, recognising the existence of competing events is highly relevant to the sampling of control probands. Because of the presence of multiple family members who may be censored at different ages, the estimation of inverse probability of censoring weights is not as straightforward as in the twin setting but requires consideration. We propose to employ a composite likelihood conditioning on proband status that markedly simplifies adjustment for right censoring. We assess the proposed approach using simulation studies and apply it in the analysis of two Danish register-based case-control-family studies: one on cancer diagnosed in childhood and adolescence, and one on early-onset breast cancer. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Section of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, POB 2099, Copenhagen K, DK-1014, Denmark.|Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen Ø, DK-2100, Denmark.
authors.forename: Luise
authors.identifier: 0000-0002-7601-9723
authors.initials: L
authors.lastname: Cederkvist
authors.affiliation: Section of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, POB 2099, Copenhagen K, DK-1014, Denmark.
authors.forename: Klaus K
authors.initials: KK
authors.lastname: Holst
authors.affiliation: Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen Ø, DK-2100, Denmark.
authors.forename: Klaus K
authors.initials: KK
authors.lastname: Andersen
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, 550 16th Street, 2nd floor, San Francisco, CA, 94158, U.S.A.
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.affiliation: Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen Ø, DK-2100, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Frederiksen
authors.affiliation: Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen Ø, DK-2100, Denmark.|Department of Gynecology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen Ø, DK-2100, Denmark.
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
authors.affiliation: Section of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, POB 2099, Copenhagen K, DK-1014, Denmark.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Scheike
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D056808:Biostatistics; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D003198:Computer Simulation; D003718:Denmark / Q000453:epidemiology; D005190:Family; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D010375:Pedigree; D011336:Probability; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
keywords: case-control-family study; competing risks; composite likelihood; inverse probability of censoring weighting; liability-threshold model