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An exponential increase in QTL detection with an increased sample size.

Apurva S Chitre1, Oksana Polesskaya1, Daniel Munro1,2

  • 1Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.

Genetics
|March 28, 2023
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Summary

Larger sample sizes in genome-wide association studies (GWAS) exponentially increase the number of significant loci discovered. Future rodent GWAS should use larger sample sizes to maximize discovery of significant genetic loci.

Keywords:
GWASQTLheterogeneous stock (HS) ratssample size

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Area of Science:

  • Genetics
  • Statistical Genetics
  • Animal Models

Background:

  • Power analyses commonly determine sample size for genome-wide association studies (GWAS) to detect at least one significant locus.
  • The relationship between sample size and the number of significant loci discovered is less frequently explored.

Purpose of the Study:

  • To investigate the impact of sample size on the number of significant loci identified in rodent GWAS.
  • To explore the relationship between sample size and trait heritability in discovering significant loci.

Main Methods:

  • Simulations were performed using a dataset of 3,173 N/NIH heterogeneous stock rats.
  • Data were subsampled to various sizes (500 to 2,500) for 4 traits with differing SNP-based heritabilities.
  • Subsampling was repeated 100 times for each sample size and trait combination.

Main Results:

  • An exponential increase in the number of significant loci discovered was observed with larger sample sizes.
  • The number of significant loci identified was influenced by both sample size and trait heritability.
  • Results align with findings from human GWAS, indicating a similar pattern.

Conclusions:

  • Rodent GWAS require substantially larger sample sizes than typically used to achieve single-locus significance.
  • Increasing sample size is crucial for maximizing the discovery of multiple significant genetic loci in GWAS.
  • These findings have implications for the design and power calculations of future rodent genetic studies.