Using Summary Statistics to Model Multiplicative Combinations of Initially Analyzed Phenotypes With a Flexible Choice of Covariates.
covariate adjustment
linear models
multiplication
phenotype
summary statistics
Journal
Frontiers in genetics
ISSN: 1664-8021
Titre abrégé: Front Genet
Pays: Switzerland
ID NLM: 101560621
Informations de publication
Date de publication:
2021
2021
Historique:
received:
22
07
2021
accepted:
23
09
2021
entrez:
29
10
2021
pubmed:
30
10
2021
medline:
30
10
2021
Statut:
epublish
Résumé
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 ratios of fatty acids 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.
Identifiants
pubmed: 34712269
doi: 10.3389/fgene.2021.745901
pii: 745901
pmc: PMC8546319
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
745901Subventions
Organisme : NHGRI NIH HHS
ID : R15 HG006915
Pays : United States
Informations de copyright
Copyright © 2021 Wolf , Westra and Tintle.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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