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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

Panagiota Kyratzi

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