154: Multiple-testing corrections in IBD-based selection scans

Temple SD et al., The American Journal of Human Genetics - Temple and Browning model correlations of identity-by-descent (IBD) rates to derive analytical and simulation-based genome-wide significance thresholds for selection scans, apply these to TOPMed and UK Biobank cohorts, and show many signals cluster near structural-variant hotspots. Key terms: identity-by-descent, selection scans, multiple testing, Ornstein-Uhlenbeck, population genetics. Study Highlights:The authors model standardized IBD rates along chromosomes as an Ornstein-Uhlenbeck process to obtain analytical and simulation-based multiple-testing thresholds that account for test spacing. In whole-genome simulations the methods approximately control the family-wise error rate, with the ≽5.3 cM scan tending toward anti-conservative behavior and the ≽6.3 cM scan conservative. Power exceeds 50% for hard sweeps with selection coefficients ≥0.01 at intermediate present-day allele frequencies. Applying the corrected thresholds to TOPMed and UKBB reduced the number of candidate loci and revealed shared excess-IBD regions enriched for structural variants. Conclusion:Modeling genomic autocorrelation of IBD rates yields practical multiple-testing corrections that reduce false positives in recent-selection scans, but interpretation must consider structural variation, demographic effects, and limitations of the OU approximation. Music:Enjoy the music based on this article at the end of the episode. Article title:Multiple-testing corrections in selection scans using identity-by-descent segments First author:Temple SD Journal:The American Journal of Human Genetics DOI:10.1016/j.ajhg.2025.09.004 Reference:Temple SD, Browning SR. Multiple-testing corrections in selection scans using identity-by-descent segments. Am J Hum Genet. 2025;112:1–21. doi:10.1016/j.ajhg.2025.09.004 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/multiple-testing-corrections-in-selection-scans-using-identity-by-descent-segments QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-10-01. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited sections describing the OU process modeling of IBD rates, the analytical Siegmund–Yakir approximation, the simulation-based thresholds, the power for hard sweeps, and the empirical findings including LCT, OCA2, HBB signals and the structural-variant mirages near XYLT1 and 22q11.21.- transcript topics: Genome pattern recognition and IBD sharing; Identity-by-descent segments and selection scans; Multiple-testing corrections and FWER; Ornstein–Uhlenbeck process modeling of IBD rates; Analytical (Siegmund–Yakir) and simulation-based thresholds; Power to detect hard sweeps QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 7- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- Model OU process to derive genome-wide significance for IBD-based scans- Analytical Siegmund–Yakir approximation and simulation-based thresholds