Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping

Kyratzi, Panagiota; Matika, Oswald; Brassington, Amey H; Connie, Clare E; Xu, Juan; Barrett, David A; Emes, Richard D; Archibald, Alan L; Paldi, Andras; Sinclair, Kevin D; Wattis, Jonathan; Rauch, Cyril

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 ovis aries 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., Connie, C. E., Xu, J., Barrett, D. A., Emes, R. D., Archibald, A. L., Paldi, A., Sinclair, K. D., Wattis, J., & Rauch, C. Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping

• Working Paper Type: Preprint
• Deposit Date: Sep 4, 2024
• Publicly Available Date: Oct 10, 2024
• DOI: https://doi.org/10.1101/2024.04.16.589524
• Public URL: https://nottingham-repository.worktribe.com/output/33839072
• Publisher URL: https://www.biorxiv.org/content/10.1101/2024.04.16.589524v2
• Additional Information: Preprint which has not been peer reviewed.