| Title: | Multiple-testing corrections in selection scans using identity-by-descent segments |
| Journal: | American Journal of Human Genetics |
| Published: | 26 Sep 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41015036/ |
| DOI: | https://doi.org/10.1016/j.ajhg.2025.09.004 |
Publication 19408
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Abstract
Failing to correct for multiple testing in selection scans can lead to false discoveries of recent genetic adaptations. The scanning statistics in selection studies are often too complicated to theoretically derive a genome-wide significance level or empirically validate control of the family-wise error rate (FWER). By modeling the autocorrelation of identity-by-descent (IBD) rates, we propose a computationally efficient method to determine genome-wide significance levels in an IBD-based scan for recent positive selection. In whole-genome simulations, we show that our method has approximate control of the FWER and can adapt to the spacing of tests along the genome. We also show that these scans can have more than 50% power to reject the null model in hard sweeps with a selection coefficient greater than or equal to 0.01 and a sweeping allele frequency between 25% and 75%. Many human genes and gene complexes have statistically significant excesses of IBD segments in thousands of samples of African, European, and South Asian ancestry groups from the Trans-Omics for Precision Medicine project and the United Kingdom Biobank. Among the significant loci, two excess IBD signals in regions enriched for deletions are shared across ancestry groups.</p>
8 Keywords
- Computer Simulation
- Gene Frequency
- Genome, Human
- Genome-Wide Association Study
- Humans
- Models, Genetic
- Polymorphism, Single Nucleotide
- Selection, Genetic
2 Authors
- Seth D. Temple
- Sharon R. Browning
1 Application
| Application ID | Title |
|---|---|
| 19934 | Statistical and Computational Genetics Methods Development |
Enabling scientific discoveries that improve human health