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Multiple-testing corrections in selection scans using identity-by-descent segments.

Seth D Temple1, Sharon R Browning2

  • 1Department of Statistics, University of Washington, Seattle, WA, USA; Department of Statistics, University of Michigan, Ann Arbor, MI, USA; Michigan Institute for Data and AI in Society, University of Michigan, Ann Arbor, MI, USA.

American Journal of Human Genetics
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Summary
This summary is machine-generated.

Correcting for multiple testing in genetic adaptation scans is crucial to avoid false discoveries. This study introduces an efficient method using identity-by-descent (IBD) modeling to accurately determine genome-wide significance levels for detecting recent positive selection.

Keywords:
identity by descentmean-reverting processesmultiple testingnatural selection

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Area of Science:

  • Population Genetics
  • Genomics
  • Evolutionary Biology

Background:

  • Multiple testing in selection scans can lead to false discoveries of genetic adaptations.
  • Deriving genome-wide significance levels and validating family-wise error rate (FWER) control is challenging due to complex scanning statistics.

Purpose of the Study:

  • To propose a computationally efficient method for determining genome-wide significance levels in identity-by-descent (IBD)-based scans for recent positive selection.
  • To address the challenges of multiple testing correction in detecting genetic adaptations.

Main Methods:

  • Modeling the autocorrelation of identity-by-descent (IBD) rates.
  • Developing a method to determine genome-wide significance levels for IBD-based scans.
  • Utilizing whole-genome simulations to validate the method's performance.

Main Results:

  • The proposed method demonstrates approximate control of the family-wise error rate (FWER).
  • The method adapts to the spacing of tests across the genome.
  • Scans achieved over 50% power to detect hard sweeps with a selection coefficient >= 0.01 and allele frequency between 25-75%.

Conclusions:

  • The study successfully identified statistically significant excesses of IBD segments in human genes across diverse ancestry groups (African, European, South Asian).
  • Two shared IBD excess signals in deletion-enriched regions were found across ancestry groups, suggesting potential common adaptive events.