Family-based Methods for Linkage and Association Analysis

Traditional epidemiological study concepts such as case-control or cohort designs can be used in the design of genetic association studies, giving them a prominent role in genetic association analysis. A different class of designs based on related individuals, typically families, uses the concept of Mendelian transmission to achieve design-independent randomization, which permits the testing of linkage and association. Family-based designs require specialized analytic methods but they have distinct advantages: They are robust to confounding and variance inflation, which can arise in standard designs in the presence of population substructure; they test for both linkage and association; and they offer a natural solution to the multiple comparison problem. This chapter focuses on family-based designs. We describe some basic study designs as well as general approaches to analysis for qualitative, quantitative, and complex traits. Finally, we review available software.