Panagiota Kyratzi
Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping.
Kyratzi, Panagiota; Matika, Oswald; Brassington, Amey H; Clare, Connie E; Xu, Juan; Barrett, David A; Emes, Richard D; Archibald, Alan L; Paldi, Andras; Sinclair, Kevin D; Wattis, Jonathan; Rauch, Cyril
Authors
Oswald Matika
Amey H Brassington
Connie E Clare
Juan Xu
David A Barrett
Richard D Emes
Alan L Archibald
Andras Paldi
KEVIN SINCLAIR kevin.sinclair@nottingham.ac.uk
Professor of Developmental Biology
JONATHAN WATTIS jonathan.wattis@nottingham.ac.uk
Professor of Applied Mathematics
CYRIL RAUCH CYRIL.RAUCH@NOTTINGHAM.AC.UK
Associate Professor
Abstract
Identifying associations between phenotype and genotype is the fundamental basis of genetic analyses. Inspired by frequentist probability and the work of R.A. Fisher, genome-wide association studies (GWAS) extract information using averages and variances from genotype-phenotype datasets. Averages and variances are legitimated upon creating distribution density functions obtained through the grouping of data into categories. However, as data from within a given category cannot be differentiated, the investigative power of such methodologies is limited. Genomic Informational Field Theory (GIFT) is a method specifically designed to circumvent this issue. The way GIFT proceeds is opposite to that of GWAS. Whilst GWAS determines the extent to which genes are involved in phenotype formation (bottom-up approach), GIFT determines the degree to which the phenotype can select microstates (genes) for its subsistence (top-down approach). Doing so requires dealing with new genetic concepts, a.k.a. genetic paths, upon which significance levels for genotype-phenotype associations can be determined. By using different datasets obtained in related to bone growth (Dataset-1) and to a series of linked metabolic and epigenetic pathways (Dataset-2), we demonstrate that removing the informational barrier linked to categories enhances the investigative and discriminative powers of GIFT, namely that GIFT extracts more information than GWAS. We conclude by suggesting that GIFT is an adequate tool to study how phenotypic plasticity and genetic assimilation are linked.
Citation
Kyratzi, P., Matika, O., Brassington, A. H., Clare, C. E., Xu, J., Barrett, D. A., Emes, R. D., Archibald, A. L., Paldi, A., Sinclair, K. D., Wattis, J., & Rauch, C. (in press). Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping. Physiological Genomics, https://doi.org/10.1152/physiolgenomics.00049.2024
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 3, 2024 |
Online Publication Date | Sep 9, 2024 |
Deposit Date | Oct 10, 2024 |
Print ISSN | 1094-8341 |
Electronic ISSN | 1531-2267 |
Publisher | American Physiological Society |
Peer Reviewed | Peer Reviewed |
DOI | https://doi.org/10.1152/physiolgenomics.00049.2024 |
Keywords | Complex traits, GWAS, genotype-phenotype mapping studies, GIFT |
Public URL | https://nottingham-repository.worktribe.com/output/39978520 |
Publisher URL | https://journals.physiology.org/doi/abs/10.1152/physiolgenomics.00049.2024 |
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