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Biostatistics 3:315-329 (2002)
© 2002 Oxford University Press

Combined association, segregation and aggregation analysis on case–control family data

Lue Ping Zhao, Ori Davidov, Filemon Quiaoit, Li Hsu and Sarah Holte

Lue Ping Zhao. Quantitative Genetic Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA, USA
Ori Davidov. Department of Statistics, University of Haifa, Mount Carmel, Haifa 31905, Israel
Filemon Quiaoit, Li Hsu, Sarah Holte. Quantitative Genetic Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA, USA

Recently genetic epidemiologists have begun using case–control family study designs to investigate the role of genetic and environmental risk factors in disease etiology. The objective of these studies is to assess the association of environmental factors with the disease trait; to characterize the disease genes using segregation analysis; and to quantify the residual familial aggregation after controlling for environmental and genetic factors. Typically these objectives are achieved by conducting separate studies and analysis. This paper describes an estimating equation based approach for a combined association, segregation and aggregation analysis on data from case–control family studies. Simulations indicate that the method performs well in a variety of settings. The method is illustrated using simulated family history data made available to participants in a recent Genetic Analysis Workshop.

Keywords: Aggregation; Association; Case–control family studies; Efficient estimating equations; Segregation


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