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. 2020 Feb 4;117(5):2710-2716.
doi: 10.1073/pnas.1913179117. Epub 2020 Jan 21.

Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases

Affiliations

Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases

Mor Hanany et al. Proc Natl Acad Sci U S A. .

Abstract

One of the major questions in human genetics is what percentage of individuals in the general population carry a disease-causing mutation. Based on publicly available information on genotypes from six main world populations, we created a database including data on 276,921 sequence variants, present within 187 genes associated with autosomal recessive (AR) inherited retinal diseases (IRDs). Assessment of these variants revealed that 10,044 were categorized as disease-causing mutations. We developed an algorithm to compute the gene-specific prevalence of disease, as well as the mutational burden in healthy subjects. We found that the genetic prevalence of AR-IRDs corresponds approximately to 1 case in 1,380 individuals, with 5.5 million people expected to be affected worldwide. In addition, we calculated that unaffected carriers of mutations are numerous, ranging from 1 in 2.26 individuals in Europeans to 1 in 3.50 individuals in the Finnish population. Our analysis indicates that about 2.7 billion people worldwide (36% of the population) are healthy carriers of at least one mutation that can cause AR-IRD, a value that is probably the highest across any group of Mendelian conditions in humans.

Keywords: carrier frequency; disease-causing mutation; genetic prevalence; human genome; inherited retinal diseases.

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Conflict of interest statement

The authors declare no competing interest.

Figures

Fig. 1.
Fig. 1.
Flowchart showing the analytical scheme for the variants downloaded from gnomAD.
Fig. 2.
Fig. 2.
AR-IRD CF and GP per subpopulation worldwide. CF is depicted by the purple bars and measured by the left vertical axis. The dark purple area of each bar represents the contribution of ABCA4 hypomorphic variants. GP is depicted by the dark blue bars (right vertical axis).
Fig. 3.
Fig. 3.
Pie charts showing (A) the expected disease prevalence per gene worldwide and (B) the fraction of expected affected cases per diagnostic class out of all AR-IRD cases. ACHM, achromatopsia; SLS, Senior-Loken syndrome.
Fig. 4.
Fig. 4.
Worldwide distribution of healthy WT individuals, healthy AR-IRD carriers, and expected affected individuals. The numbers displayed are the number of individuals in each group.

Comment in

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