Overview of linkage analysis in complex traits

Abstract

Linkage analysis is a well-established and powerful method for mapping disease genes. While linkage analysis has been most successful when applied to disorders with clear patterns of Mendelian inheritance, it can also be a useful technique for mapping susceptibility genes for common complex diseases. In this unit, we outline the key concepts of complex disease, and how linkage analysis for complex traits differs from simple Mendelian traits. Optimal genetic studies require careful study design, ascertainment strategy, and analysis methods. We describe how disease parameters such as prevalence, heritability estimates, and mode of inheritance should be considered before data is collected. Furthermore, we outline a general strategic approach for conducting linkage analysis of a complex disease, along with several design considerations that can optimize statistical power to detect disease loci and generally improve the quality of a study. Finally, we discuss the benefits and weaknesses of linkage analysis in contrast to genome-wide association studies.