Haplotype sharing analysis in affected individuals from nuclear families with at least one affected offspring

In diseases with a complex mode of inheritance, families with multiple affected individuals are difficult to ascertain. The haplotype sharing statistic (HSS) uses (hidden) co-ancestry between affected individuals from a founder population. These affected individuals will likely not only share the same mutation(s), but also the surrounding haplotype. We show that this method gives a low false positive rate, but does not detect genes in the nuclear families of Problem 2A of the GAW data. We also give evidence based on simulations and empirical studies in real population based data that the HSS method has statistical power.