Fine-scale genetic structure and rare variant frequencies.

In response to the current challenge in genetic studies to make new associations, we advocate for a shift toward leveraging population fine-scale structure. Our exploration brings to light distinct fine-structure within populations having undergone a founder effect such as the Ashkenazi Jews and the population of the Quebec' province. We leverage the fine-scale population structure to explore its impact on the frequency of rare variants. Notably, we observed an 8-fold increase in frequency for a variant associated with the Usher syndrome in one Quebec subpopulation. Our study underscores that smaller cohorts with greater genetic similarity demonstrate an important increase in rare variant frequencies, offering a promising avenue for new genetic variants' discovery.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Gagnon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)