Considerations in the search for epistasis

Соображения по поиску эпистаза
Marleen Balvert, Johnathan Cooper‐Knock, Julian Stamp, Ross P. Byrne, Soufiane Mourragui, Juami H. M. van Gils, Stefania Benónísdóttir, Johannes Schlüter, Kevin P. Kenna, Sanne Abeln, Alfredo Iacoangeli, Joséphine T. Daub, Brian L. Browning, Gizem Taş, Jiajing Hu, Yan Wang, Elham Alhathli, Calum Harvey, Luna Pianesi, Sara C. Schulte, Jorge González-Domínguez, Erik Garrisson, Ammar Al‐Chalabi, Jorge Avila Cartes, Jasmijn A. Baaijens, Joanna von Berg, Davide Bolognini, Paola Bonizzoni, Andrea Guarracino, Mehmet Koyutürk, Magda Markowska, Raghuram Dandinasivara, Jasper van Bemmelen, Sebastian Vorbrugg, Sai Zhang, Bogdan Pasanuic, M Snyder, Alexander Schönhuth, Letitia M.F. Sng, Natalie A. Twine, Natalie A. Twine, Lorentz workshop on epistasis, Johannes Schlüter, Joanna von Berg
2024-11-19

additive heritability modelepistasisgenetic interactionsmissing heritabilitysingle nucleotide polymorphism
Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability. We identify key challenges and propose that future works need to leverage idealized systems, known biology and even previously identified epistatic interactions, in order to guide the search for new interactions.
1
Despite its biological plausibility, the search for epistasis has largely failed to account for missing heritability.
2
Epistasis describes context-dependent genetic effects that could explain phenotypic variation beyond additive heritability models.
3
Future searches should be guided by idealized systems, established biological knowledge, and previously identified epistatic interactions.
4
Major challenges hinder the reliable detection of epistatic interactions in genetic studies.

epistatic interactions among genetic units, including single nucleotide polymorphisms and genes

the challenges and guiding principles for searching for epistasis to explain missing heritability

Publication Details
Publication Date
2024-11-19
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Authors
Marleen Balvert
Johnathan Cooper‐Knock
Julian Stamp
Ross P. Byrne
Soufiane Mourragui
Juami H. M. van Gils
Stefania Benónísdóttir
Johannes Schlüter
Kevin P. Kenna
Sanne Abeln
Alfredo Iacoangeli
Joséphine T. Daub
Brian L. Browning
Gizem Taş
Jiajing Hu
Yan Wang
Elham Alhathli
Calum Harvey
Luna Pianesi
Sara C. Schulte
Jorge González-Domínguez
Erik Garrisson
Ammar Al‐Chalabi
Jorge Avila Cartes
Jasmijn A. Baaijens
Joanna von Berg
Davide Bolognini
Paola Bonizzoni
Andrea Guarracino
Mehmet Koyutürk
Magda Markowska
Raghuram Dandinasivara
Jasper van Bemmelen
Sebastian Vorbrugg
Sai Zhang
Bogdan Pasanuic
M Snyder
Alexander Schönhuth
Letitia M.F. Sng
Natalie A. Twine
Natalie A. Twine
Lorentz workshop on epistasis
Johannes Schlüter
Joanna von Berg
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