Clinical genomics can facilitate countrywide estimation of autosomal recessive disease burden

Abstract

Background:Most autosomal recessive diseases are rare, but they collectively account for a substantial proportion of disease burden, especially in consanguineous populations. Estimation of this disease burden, however, is hampered by many factors, including lack of countrywide registries. Establishing carrier frequency can be a practical surrogate to estimate disease burden, although the requirement of a large representative cohort may be challenging.Purpose:We propose that the application of clinical genomics in the diagnostic setting offers a unique opportunity to estimate carrier frequency in the population as a secondary benefit.Methods:We used a data set of ∼7,100 patients who underwent genomic testing for various Mendelian disorders to estimate the carrier frequency.Results:We were able to calculate the frequency of 259 confirmed founder recessive mutations. We found the corresponding disease burden to be, at minimum, ∼7 per 1,000 children born to first-cousin parents, with disorders related to intellectual disability and vision impairment being the most common.Conclusion:Our approach can be utilized to inform the design of new policies for the prevention of genetic disorders and highlights an important secondary benefit of clinical genomics.