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Epistasis Analysis

Epistasis Analysis

Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...

Polygenic Traits

Polygenic Traits

When more than one gene is responsible for a given phenotype, the trait is considered polygenic. Human height is a polygenic trait. Studies have uncovered hundreds of loci that influence height, and there are believed to be many more. Due to the high number of genes involved, as well as environmental and nutritional factors, height varies significantly within a given population. The distribution of height forms a bell-shaped curve, with relatively few individuals in the population at the...

Epistasis

Epistasis

In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...

Multiple Allele Traits

Multiple Allele Traits

The Concept of Multiple Allelism

Pleiotropy

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...

Incomplete Dominance

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.

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Related Experiment Video

Updated: Nov 9, 2025

Large-Scale Multi-Omics Genome-Wide Association Studies Mo-GWAS: Guidelines for Sample Preparation and Normalization

Large-Scale Multi-Omics Genome-Wide Association Studies Mo-GWAS: Guidelines for Sample Preparation and Normalization

Published on: July 27, 2021

A model and test for coordinated polygenic epistasis in complex traits.

Brooke Sheppard¹, Nadav Rappoport^1,2, Po-Ru Loh^3,4

¹Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94143.

Proceedings of the National Academy of Sciences of the United States of America

|April 9, 2021

Summary

This summary is machine-generated.

We introduce coordinated epistasis (CE), a new model for genetic interactions, and show it explains complex human traits. Our findings reveal systemic epistasis in 18 of 26 UK Biobank traits.

Keywords:

epistasis genetics polygenic risk

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Area of Science:

Genetics
Bioinformatics
Computational Biology

Background:

Epistasis, or gene-gene interactions, significantly influences complex traits but is often modeled simplistically.
Existing models typically assume independence between epistasis and main genetic effects, potentially missing crucial biological mechanisms.

Purpose of the Study:

To develop and validate a novel model for structured polygenic epistasis, termed coordinated epistasis (CE).
To demonstrate that CE encompasses several existing theories of genetic architecture.
To empirically test for CE in human complex traits and explore its tissue-specific manifestations.

Main Methods:

Development of the coordinated epistasis (CE) model, which captures systematic correlations between epistasis and main genetic effects.
Introduction of the even-odd (EO) test to detect CE, with theoretical calibration in diverse biological models.
Application of the EO test to UK Biobank data for 26 human traits and extension to tissue-specific enrichment analysis.

Main Results:

The CE model provides a unifying framework for several recent genetic architecture theories.
The EO test is robustly calibrated across various biological models.
Evidence for CE was found in 18 out of 26 diverse human traits (disease, anthropometric, blood).
Tissue-specific enrichment analysis identified plausible tissue-trait associations for CE.

Conclusions:

Coordinated epistasis (CE) represents a significant, previously underappreciated dimension of genetic architecture in complex human traits.
The developed EO test offers a powerful tool for detecting structured epistasis in large-scale genetic datasets.
Understanding CE has implications for evolutionary adaptation, disease dynamics, genetic mapping, and precision medicine.