Genetically informative study designs have long been of great importance for helping to determine the role the environment and genetic susceptibility play in several human phenotypes. Of such designs, one of the most well-known is the classical twin design, including both monozygotic (MZ) and dizygotic (DZ) participants. In addition to the comparison of MZ and DZ twin pairs, studies focused on MZ twin pairs discordant for a specific phenotype allow for researchers to better understand how environmental influences impact a trait while controlling for the host genomic profile. Beyond the use of twin derived samples, with information on the genomic content of unrelated individuals, it is possible to create genetically informative designs aimed at understanding many biological phenomena.