Methods for linkage analysis of complex genetic disease.

Abstract

The identification of genes playing a role in the etiology of common diseases, such as diabetes, mental illness, and heart disease could have substantial impact on the prevention, diagnosis and treatment of these diseases and could reduce the burden of these disease on the public health. Consequently, the development of statistical methods for genetic analysis of complex genetic traits is a very active area of research in human genetics. This dissertation describes the development of statistical methods for the genetic linkage analysis of complex genetic traits using affected sibling pairs and examines the performance of these methods in simulation studies. The dissertation is presented as a series of four papers: (1) description of an interval mapping method for genetic linkage analysis; (2) extension of the interval mapping method to a multipoint (multiple markers) method; (3) examination of the robustness of the multipoint method to misspecification of the marker map; and (4) an investigation of the performance of the multipoint method when attempting to confirm a linkage result in an independent population.