The analyses described so far assume that subjects are unrelated. If the study is family based, the analysis has to take into account the correlation between relatives due to their common genetic background. Different approaches have been proposed to account for the family structure. A class of methods known as family based association tests (FBAT) is commonly used in GWAS and reviewed in detail in [50]. The FBAT generalizes the transmission disequilibrium test (TDT) that was introduced in [73] to test for linkage and association in family trios (two parents and an affected child). The intuition of the TDT is to compare the number of alleles that are transmitted to affected offspring from unaffected parents with those expected under the null hypothesis of no association between genotype and phenotype. The method was generalized to accommodate sibships [74], missing genotypes [75], and to include both related and unrelated subjects [76–78]. The FBAT generalizes the TDT by computing the covariance between genotype and phenotype that are centered in such a way to accommodate different sampling designs. The method can be used to
