The approach has been successfully used to study several quantitative traits in a sample of closely related individuals from four villages in Sardinia (77). Among study participants, 1,412 individuals were genotyped with the Affymetrix mapping array set (which assays ~500,000 SNPs) and a further 3,329 individuals were genotyped with Affymetrix 10K SNP mapping arrays (which assay ~10,000 SNPs) (94). The sample was then used to study the genetic architecture of a variety of quantitative traits, ranging from body mass index (94) to fetal hemoglobin levels (106) to personality traits (101). Clearly family based genotype imputation will be maximally useful in samples that include very large numbers of related individuals. In these settings, genotypes for a relatively modest number of individuals can be propagated to many other additional individuals, increasing power. Still, in our view, imputing genotypes for known relatives of the individuals included in a genomewide association scan will always increase power (15) and should be considered whenever individuals to be genotyped in a scan are selected from a larger sample of related individuals previously collected to facilitate linkage analyses or family-based association testing.
