Unequal representation of genetic variation across ancestry groups creates healthcare inequality in the application of precision medicine

Abstract

An important application of modern genomics is diagnosing genetic disorders. We use the largest publicly available exome sequence database to show that this key clinical service can currently be performed much more effectively in individuals of European genetic ancestry.

Keywords: Clinical diagnostics; Disease-associated genes; Genetic ancestry; Genetic variation; Geographic ancestry; Healthcare inequality; Next generation sequencing; Precision medicine; Rare variants; Sequence interpretation.

Fig. 1

a Percentage representation of the 5965 IGM reference cohort across six geographic ancestry groupings. b A semi-transparent overlaid histogram representing the tally of candidate variants between IGM’s 5094 European (Eu) individuals (blue) and the collection of non-European individuals (red) (Mann–Whitney U test p < 1 × 10⁻³²⁰). The non-European distribution reflects individuals with a: Latino ethnicity (La), East Asian (EaAs), South Asian (SoAs), primarily African (Af), and unassigned (Un) ancestry. Estimates indicate the mean number of singleton non-synonymous variants among OMIM disease-associated genes. Singleton variants are identified based on a reference cohort of 5965 IGM sequenced samples. c Percentage representation of the combined 66,217 IGM and ExAC reference cohorts across six geographic ancestry / ethnic groupings. d Similar to b but singleton variants were identified based on the absence among the combined IGM and ExAC reference cohorts accumulating to 66,217 samples