The theoretical case for a significant role of rare variants is that alleles that strongly predispose an individual to disease will be kept at low frequencies in populations by purifying selection.
[2] Rare variants are increasingly being studied, as a consequence of whole exome and whole genome sequencing efforts.
They are more likely to be deleterious than common variants, as a result of rapid population growth and weak purifying selection.
These methods may increase power when multiple variants in the region are associated with a disease or a trait.
[10] SNP annotations help to prioritize rare functional variants, and incorporating these annotations can effectively boost the power of genetic association of rare variants analysis of whole exome and whole genome sequencing studies.