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Exponential increase in QTL detection with increased sample size

View ORCID ProfileApurva S. Chitre, Oksana Polesskaya, Daniel Munro, Riyan Cheng, View ORCID ProfilePejman Mohammadi, Katie Holl, Jianjun Gao, View ORCID ProfileHannah Bimschleger, Angel Garcia Martinez, Anthony George, View ORCID ProfileAlexander F. Gileta, Aidan Horvath, Alesa Hughson, Keita Ishiwari, Christopher P. King, Alexander Lamparelli, Cassandra L. Versaggi, Connor Martin, View ORCID ProfileCeline L. St. Pierre, Jordan A. Tripi, Jerry B. Richards, Tengfei Wang, View ORCID ProfileHao Chen, Shelly B. Flagel, Paul Meyer, Terry E. Robinson, Leah C. Solberg Woods, View ORCID ProfileAbraham A. Palmer
doi: https://doi.org/10.1101/2023.01.27.525982
Apurva S. Chitre
1Department of Psychiatry, University of California San Diego
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Oksana Polesskaya
1Department of Psychiatry, University of California San Diego
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Daniel Munro
1Department of Psychiatry, University of California San Diego
13Department of Integrative Structural and Computational Biology, Scripps Research
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Riyan Cheng
1Department of Psychiatry, University of California San Diego
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Pejman Mohammadi
13Department of Integrative Structural and Computational Biology, Scripps Research
14Scripps Research Translational Institute, Scripps Research
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Katie Holl
2Human and Molecular Genetic Center, Medical College of Wisconsin
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Jianjun Gao
1Department of Psychiatry, University of California San Diego
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Hannah Bimschleger
1Department of Psychiatry, University of California San Diego
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Angel Garcia Martinez
3Department of Pharmacology, University of Tennessee Health Science Center
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Anthony George
6Clinical and Research Institute on Addictions, University at Buffalo
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Alexander F. Gileta
1Department of Psychiatry, University of California San Diego
10Department of Human Genetics, University of Chicago
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  • ORCID record for Alexander F. Gileta
Aidan Horvath
4Department of Psychiatry, University of Michigan
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Alesa Hughson
4Department of Psychiatry, University of Michigan
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Keita Ishiwari
6Clinical and Research Institute on Addictions, University at Buffalo
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Christopher P. King
5Department of Psychology, University at Buffalo
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Alexander Lamparelli
5Department of Psychology, University at Buffalo
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Cassandra L. Versaggi
5Department of Psychology, University at Buffalo
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Connor Martin
6Clinical and Research Institute on Addictions, University at Buffalo
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Celine L. St. Pierre
11Department of Genetics, Washington University in St. Louis
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Jordan A. Tripi
5Department of Psychology, University at Buffalo
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Jerry B. Richards
6Clinical and Research Institute on Addictions, University at Buffalo
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Tengfei Wang
3Department of Pharmacology, University of Tennessee Health Science Center
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Hao Chen
3Department of Pharmacology, University of Tennessee Health Science Center
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Shelly B. Flagel
12Molecular and Behavioral Neuroscience Institute, University of Michigan
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Paul Meyer
5Department of Psychology, University at Buffalo
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Terry E. Robinson
7Department of Psychology, University of Michigan
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Leah C. Solberg Woods
9Department of Internal Medicine, Wake Forest School of Medicine
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Abraham A. Palmer
1Department of Psychiatry, University of California San Diego
8Institute for Genomic Medicine, University of California San Diego
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  • ORCID record for Abraham A. Palmer
  • For correspondence: aapalmer@health.ucsd.edu
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Abstract

Power analyses are often used to determine the number of animals required for a genome wide association analysis (GWAS). These analyses are typically intended to estimate the sample size needed for at least one locus to exceed a genome-wide significance threshold. A related question that is less commonly considered is the number of significant loci that will be discovered with a given sample size. We used simulations based on a real dataset that consisted of 3,173 male and female adult N/NIH heterogeneous stock (HS) rats to explore the relationship between sample size and the number of significant loci discovered. Our simulations examined the number of loci identified in sub-samples of the full dataset. The sub-sampling analysis was conducted for four traits with low (0.15 ± 0.03), medium (0.31 ± 0.03 and 0.36 ± 0.03) and high (0.46 ± 0.03) SNP-based heritabilities. For each trait, we sub-sampled the data 100 times at different sample sizes (500, 1,000, 1,500, 2,000, and 2,500). We observed an exponential increase in the number of significant loci with larger sample sizes. Our results are consistent with similar observations in human GWAS and imply that future rodent GWAS should use sample sizes that are significantly larger than those needed to obtain a single significant result.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 29, 2023.
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Exponential increase in QTL detection with increased sample size
Apurva S. Chitre, Oksana Polesskaya, Daniel Munro, Riyan Cheng, Pejman Mohammadi, Katie Holl, Jianjun Gao, Hannah Bimschleger, Angel Garcia Martinez, Anthony George, Alexander F. Gileta, Aidan Horvath, Alesa Hughson, Keita Ishiwari, Christopher P. King, Alexander Lamparelli, Cassandra L. Versaggi, Connor Martin, Celine L. St. Pierre, Jordan A. Tripi, Jerry B. Richards, Tengfei Wang, Hao Chen, Shelly B. Flagel, Paul Meyer, Terry E. Robinson, Leah C. Solberg Woods, Abraham A. Palmer
bioRxiv 2023.01.27.525982; doi: https://doi.org/10.1101/2023.01.27.525982
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Exponential increase in QTL detection with increased sample size
Apurva S. Chitre, Oksana Polesskaya, Daniel Munro, Riyan Cheng, Pejman Mohammadi, Katie Holl, Jianjun Gao, Hannah Bimschleger, Angel Garcia Martinez, Anthony George, Alexander F. Gileta, Aidan Horvath, Alesa Hughson, Keita Ishiwari, Christopher P. King, Alexander Lamparelli, Cassandra L. Versaggi, Connor Martin, Celine L. St. Pierre, Jordan A. Tripi, Jerry B. Richards, Tengfei Wang, Hao Chen, Shelly B. Flagel, Paul Meyer, Terry E. Robinson, Leah C. Solberg Woods, Abraham A. Palmer
bioRxiv 2023.01.27.525982; doi: https://doi.org/10.1101/2023.01.27.525982

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