Ethnic disparities in diagnostic sequencing yield
Reviewed by Ian Reekie

The authors present a systematic review and meta-analysis of the diagnostic yield of next generation sequencing (NGS) for inherited retinal diseases and compare yield from studies performed primarily on patients of European descent from those primarily of East Asian descent. Data from 42 separate studies were included: 26 European centres, 14 East Asian centres and two Latin American centres. The rate of positive genetic diagnosis was compared. The key result was that European studies (presumed to be reporting predominantly European descent patients) had a higher molecular diagnosis rate than those from East Asia, and a lower rate of inconclusive diagnosis. This held for both widely defined inherited retinal disease panels, as well as studies reporting more targeted diagnostics for specific phenotypes, e.g. Usher’s syndrome and Leber’s congenital amaurosis. These differences are stated to be significant, but the actual statistics and p values are not provided. The weaknesses of this study come principally from the method by which the authors define their categories – the studies from Europe are considered to represent patients of European descent, and studies from East Asia those of East Asian descent. There is no weighting for the actual ethnicity of the patients included within those studies. Therefore, what the authors are actually showing here is the difference in the yield from European and East Asian laboratories and using this as a proxy for the ethnicity of the patients included. The study also specifically excludes studies not written in English, which may be considered a substantial weakness when attempting to compare ethnic differences. Nonetheless, this work does focus on an extremely important issue and demonstrates that we must consider the ethnicity of our patients when interpreting the results of NGS testing. Further work needs to be done identifying pathological gene variants across multiple populations.

The ethnic disparity in the diagnostic yield of high-throughput next-generation sequencing in inherited retinal diseases: a systematic review and meta-analysis.
Lin TY, Wang CY, Chen L, Huang SP.
OPHTHALMIC GENETICS
2025;46(3):215–24.