Family-Based Genetic Association Tests

INTRODUCTION

Genetic studies in families have historically focused on tests of linkage. These tests measure the concordance between the pattern of segregation of a genetic marker allele with the occurrence of a disease phenotype within families and provide information about the amount of genetic recombination between a marker locus and a putative disease locus. Thus, linkage is a statement about transmission of gametes from parents to offspring. In contrast, association is a statement about the population of gametes. Frequencies of marker alleles in disease and nondisease individuals give us information about the amount of association, or correlation, between marker allele and disease status. Family data not only provide us information about linkage by looking at transmissions within families, but also give us information about association by looking at allelic state and the presence of disease phenotype across families. This chapter describes the evolution of family-based tests of association as well as the variety of applications for these tests.