Using family history information to distinguish true and false positive model-free linkage results

Genetic Epidemiology
J M Olson, R C Elston

Abstract

Genome scans that test for increased marker identity-by-descent sharing between pairs of affected siblings have become increasingly common. These methods do not specify a priori a genetic model for the disease locus and as such lose the ability to specify the parental source of the disease allele. We propose a method that uses family history information to build a more complete model of disease and marker inheritance, while still avoiding specification of the parameters of the disease model of inheritance. One important use for such a model is to test whether a positive linkage result obtained during the course of a genome scan is a true or false positive result. The key to the new test statistics is the interaction between gender-specific marker identity-by-descent sharing and gender-specific family history of disease. The method is useful when the disease locus of interest has a dominant mode of inheritance and a sufficient number of parents are genotyped at the marker locus. If these conditions are met, the proposed tests have good power to differentiate between true and false positive linkage results.

References

Jan 1, 1993·Genetic Epidemiology·J M Olson, E M Wijsman
Aug 1, 1997·American Journal of Human Genetics·J D TerwilligerD E Weeks

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Citations

Jul 12, 2008·BMC Medical Genetics·Richard A KerberDuncan C Thomas

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