Assessing the digenic model in rare disorders using population sequencing data

An important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases. In this case, digenic disease combinations should be absent or underrepresented in healthy individuals. We develop a framework to evaluate the significance of digenic combinations and test its statistical power in different scenarios. We suggest that this approach will be relevant with the advent of new sequencing efforts including hundreds of thousands of samples.

Bibliographic Details

Main Authors:	Moreno-Ruiz, Nerea, Lao, Oscar, Arostegui, Juan Ignacio, Laayouni, Hafid, Casals, Ferran, Genomics England Research Consortium
Other Authors:	Ministerio de Ciencia e Innovación (España)
Format:	artículo biblioteca
Language:	English
Published:	Springer Nature 2022-10-03
Subjects:	Diseases, Genetic interaction, Population genetics,
Online Access:	http://hdl.handle.net/10261/289423 http://dx.doi.org/10.13039/100004440 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100000276 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100002809 http://dx.doi.org/10.13039/501100000265 http://dx.doi.org/10.13039/501100004837 http://dx.doi.org/10.13039/501100000272 https://api.elsevier.com/content/abstract/scopus_id/85139249603
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