The allelic spectrum of disease is dependent on the number of genetic variants, their frequency in a population and on the size of their phenotypic effect. Family-based linkage studies have proved successful in identifying causative genetic variants in rare Mendelian disorders, which are, by definition, caused by highly penetrant variants that have a low frequency in the population. Complex diseases are caused by multiple genetic variants that confer incremental risk of disease. Genome-wide association studies have sufficient power to detect genetic variants with modest phenotypic effects, provided that they occur at a high frequency in the population. Adapted from .