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Using summary statistics to evaluate the genetic architecture of multiplicative combinations of initially analyzed phenotypes with a flexible choice of covariates

View ORCID ProfileJack Wolf, Jason Westra, View ORCID ProfileNathan Tintle
doi: https://doi.org/10.1101/2021.03.08.433979
Jack Wolf
1Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota
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Jason Westra
2Department of Math, Computer Science, and Statistics, Dordt University, Sioux Center, Iowa
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Nathan Tintle
2Department of Math, Computer Science, and Statistics, Dordt University, Sioux Center, Iowa
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  • For correspondence: Nathan.Tintle@dordt.edu
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Abstract

While the promise of electronic medical record and biobank data is large, major questions remain about patient privacy, computational hurdles, and data access. One promising area of recent development is pre-computing non-individually identifiable summary statistics to be made publicly available for exploration and downstream analysis. In this manuscript we demonstrate how to utilize pre-computed linear association statistics between individual genetic variants and phenotypes to infer genetic relationships between products of phenotypes (e.g., ratios; logical combinations of binary phenotypes using ‘and’ and ‘or’) with customized covariate choices. We propose a method to approximate covariate adjusted linear models for products and logical combinations of phenotypes using only pre-computed summary statistics. We evaluate our method’s accuracy through several simulation studies and an application modeling various fatty acid ratios using data from the Framingham Heart Study. These studies show consistent ability to recapitulate analysis results performed on individual level data including maintenance of the Type I error rate, power, and effect size estimates. An implementation of this proposed method is available in the publicly available R package pcsstools.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://www.ncbi.nlm.nih.gov/gap/

Copyright 
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 4.0 International license.
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Posted March 09, 2021.
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Using summary statistics to evaluate the genetic architecture of multiplicative combinations of initially analyzed phenotypes with a flexible choice of covariates
Jack Wolf, Jason Westra, Nathan Tintle
bioRxiv 2021.03.08.433979; doi: https://doi.org/10.1101/2021.03.08.433979
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Using summary statistics to evaluate the genetic architecture of multiplicative combinations of initially analyzed phenotypes with a flexible choice of covariates
Jack Wolf, Jason Westra, Nathan Tintle
bioRxiv 2021.03.08.433979; doi: https://doi.org/10.1101/2021.03.08.433979

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