Considerations in the search for epistasis

Marleen Balvert; Johnathan Cooper-Knock; Julian Stamp; Ross P. Byrne; Soufiane Mourragui; Juami van Gils; Stefania Benonisdottir; Johannes Schlüter; Kevin 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; Bogdan Pasanuic; Sai Zhang; Sebastian Vorbrugg; Jasper van Bemmelen; Raghuram Dandinasivara; Magda Markowska; Mehmet Koyuturk; Andrea Guarracino; Paola Bonizzoni; Davide Bolognini; Joanna von Berg; Jasmijn Baaijens; Jorge Avila Cartes; Ammar Al-Chalabi; Michael P. Snyder; Alexander Schönhuth; Letitia M.F. Sng; Natalie A. Twine

doi:10.1186/s13059-024-03427-z

Considerations in the search for epistasis

Marleen Balvert^*, Johnathan Cooper-Knock^*, Julian Stamp, Ross P. Byrne, Soufiane Mourragui, Juami van Gils, Stefania Benonisdottir, Johannes Schlüter, Kevin 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. SchulteJorge González-Domínguez, Erik Garrisson, Bogdan Pasanuic, Sai Zhang, Sebastian Vorbrugg, Jasper van Bemmelen, Raghuram Dandinasivara, Magda Markowska, Mehmet Koyuturk, Andrea Guarracino, Paola Bonizzoni, Davide Bolognini, Joanna von Berg, Jasmijn Baaijens, Jorge Avila Cartes, Ammar Al-Chalabi, Michael P. Snyder, Alexander Schönhuth, Letitia M.F. Sng^*, Natalie A. Twine^*,

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

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Abstract

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.

Original language	English
Article number	296
Journal	Genome Biology
Volume	25
Issue number	1
DOIs	https://doi.org/10.1186/s13059-024-03427-z
Publication status	Published - 19 Nov 2024

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Balvert, M., Cooper-Knock, J., Stamp, J., Byrne, R. P., Mourragui, S., van Gils, J., Benonisdottir, S., Schlüter, J., Kenna, K., Abeln, S., Iacoangeli, A., Daub, J. T., Browning, B. L., Taş, G., Hu, J., Wang, Y., Alhathli, E., Harvey, C., Pianesi, L. (2024). Considerations in the search for epistasis. Genome Biology, 25(1), Article 296. https://doi.org/10.1186/s13059-024-03427-z

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title = "Considerations in the search for epistasis",

abstract = "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.",

author = "Marleen Balvert and Johnathan Cooper-Knock and Julian Stamp and Byrne, \{Ross P.\} and Soufiane Mourragui and \{van Gils\}, Juami and Stefania Benonisdottir and Johannes Schl{\"u}ter and Kevin Kenna and Sanne Abeln and Alfredo Iacoangeli and Daub, \{Jos{\'e}phine T.\} and Browning, \{Brian L.\} and Gizem Ta{\c s} and Jiajing Hu and Yan Wang and Elham Alhathli and Calum Harvey and Luna Pianesi and Schulte, \{Sara C.\} and Jorge Gonz{\'a}lez-Dom{\'i}nguez and Erik Garrisson and Bogdan Pasanuic and Sai Zhang and Sebastian Vorbrugg and \{van Bemmelen\}, Jasper and Raghuram Dandinasivara and Magda Markowska and Mehmet Koyuturk and Andrea Guarracino and Paola Bonizzoni and Davide Bolognini and \{von Berg\}, Joanna and Jasmijn Baaijens and Cartes, \{Jorge Avila\} and Ammar Al-Chalabi and Snyder, \{Michael P.\} and Alexander Sch{\"o}nhuth and Sng, \{Letitia M.F.\} and Twine, \{Natalie A.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = nov,

day = "19",

doi = "10.1186/s13059-024-03427-z",

language = "English",

volume = "25",

journal = "Genome Biology",

issn = "1474-7596",

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Balvert, M, Cooper-Knock, J, Stamp, J, Byrne, RP, Mourragui, S, van Gils, J, Benonisdottir, S, Schlüter, J, Kenna, K, Abeln, S, Iacoangeli, A, Daub, JT, Browning, BL, Taş, G, Hu, J, Wang, Y, Alhathli, E, Harvey, C, Pianesi, L, Schulte, SC, González-Domínguez, J, Garrisson, E, Pasanuic, B, Zhang, S, Vorbrugg, S, van Bemmelen, J, Dandinasivara, R, Markowska, M, Koyuturk, M, Guarracino, A, Bonizzoni, P, Bolognini, D, von Berg, J, Baaijens, J, Cartes, JA, Al-Chalabi, A, Snyder, MP, Schönhuth, A, Sng, LMF, Twine, NA 2024, 'Considerations in the search for epistasis', Genome Biology, vol. 25, no. 1, 296. https://doi.org/10.1186/s13059-024-03427-z

TY - JOUR

T1 - Considerations in the search for epistasis

AU - Balvert, Marleen

AU - Cooper-Knock, Johnathan

AU - Stamp, Julian

AU - Byrne, Ross P.

AU - Mourragui, Soufiane

AU - van Gils, Juami

AU - Benonisdottir, Stefania

AU - Schlüter, Johannes

AU - Kenna, Kevin

AU - Abeln, Sanne

AU - Iacoangeli, Alfredo

AU - Daub, Joséphine T.

AU - Browning, Brian L.

AU - Taş, Gizem

AU - Hu, Jiajing

AU - Wang, Yan

AU - Alhathli, Elham

AU - Harvey, Calum

AU - Pianesi, Luna

AU - Schulte, Sara C.

AU - González-Domínguez, Jorge

AU - Garrisson, Erik

AU - Pasanuic, Bogdan

AU - Zhang, Sai

AU - Vorbrugg, Sebastian

AU - van Bemmelen, Jasper

AU - Dandinasivara, Raghuram

AU - Markowska, Magda

AU - Koyuturk, Mehmet

AU - Guarracino, Andrea

AU - Bonizzoni, Paola

AU - Bolognini, Davide

AU - von Berg, Joanna

AU - Baaijens, Jasmijn

AU - Cartes, Jorge Avila

AU - Al-Chalabi, Ammar

AU - Snyder, Michael P.

AU - Schönhuth, Alexander

AU - Sng, Letitia M.F.

AU - Twine, Natalie A.

PY - 2024/11/19

Y1 - 2024/11/19

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85210027153

U2 - 10.1186/s13059-024-03427-z

DO - 10.1186/s13059-024-03427-z

M3 - Review article

C2 - 39563431

AN - SCOPUS:85210027153

SN - 1474-7596

VL - 25

JO - Genome Biology

JF - Genome Biology

IS - 1

M1 - 296

ER -

Considerations in the search for epistasis

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Correction to: Considerations in the search for epistasis (Genome Biology, (2024), 25, 1, (296), 10.1186/s13059-024-03427-z)

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