Statistical analysis At the found genotypes from study part 3, coupling analysis is performed to identify regions in the genome shared by disease-affected individuals. The use of pedigree analysis and coupling analysis substantially reduce the candidate intervals in the genome, thereby increasing the statistical power to identify disease-causing variants even in small families. Because the precise genetic architecture and family structure of the included families is not known, exact calculation of statistical power will not be possible. In case of a dominant monogenetic disease, a filtration only based on localization (coupling) reduces the potential variants by app. 80% within a pair of affected siblings and by more than 95% for monogenetic recessive diseases, if affected individuals from inbred families.