Genetic and functional characterization of disease associations explains comorbidity

Abstract Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities betwee...

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Autores principales:	Carlota Rubio-Perez, Emre Guney, Daniel Aguilar, Janet Piñero, Javier Garcia-Garcia, Barbara Iadarola, Ferran Sanz, Narcís Fernandez-Fuentes, Laura I. Furlong, Baldo Oliva
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/38eab5823fb84a85925a9c46a44f2ef9
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spelling	oai:doaj.org-article:38eab5823fb84a85925a9c46a44f2ef92021-12-02T15:05:56ZGenetic and functional characterization of disease associations explains comorbidity10.1038/s41598-017-04939-42045-2322https://doaj.org/article/38eab5823fb84a85925a9c46a44f2ef92017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04939-4https://doaj.org/toc/2045-2322Abstract Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities between diseases. In this study, we define the disease pathways using an interactome-based extension of known disease-genes and introduce several measures of functional overlap. The analysis reveals 206 significant links among 94 diseases, giving rise to a highly clustered disease association network. We observe that around 95% of the links in the disease network, though not identified by genetic overlap, are discovered by functional overlap. This disease network portraits rheumatoid arthritis, asthma, atherosclerosis, pulmonary diseases and Crohn’s disease as hubs and thus pointing to common inflammatory processes underlying disease pathophysiology. We identify several described associations such as the inverse comorbidity relationship between Alzheimer’s disease and neoplasms. Furthermore, we investigate the disruptions in protein interactions by mapping mutations onto the domains involved in the interaction, suggesting hypotheses on the causal link between diseases. Finally, we provide several proof-of-principle examples in which we model the effect of the mutation and the change of the association strength, which could explain the observed comorbidity between diseases caused by the same genetic alterations.Carlota Rubio-PerezEmre GuneyDaniel AguilarJanet PiñeroJavier Garcia-GarciaBarbara IadarolaFerran SanzNarcís Fernandez-FuentesLaura I. FurlongBaldo OlivaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carlota Rubio-Perez Emre Guney Daniel Aguilar Janet Piñero Javier Garcia-Garcia Barbara Iadarola Ferran Sanz Narcís Fernandez-Fuentes Laura I. Furlong Baldo Oliva Genetic and functional characterization of disease associations explains comorbidity
description	Abstract Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities between diseases. In this study, we define the disease pathways using an interactome-based extension of known disease-genes and introduce several measures of functional overlap. The analysis reveals 206 significant links among 94 diseases, giving rise to a highly clustered disease association network. We observe that around 95% of the links in the disease network, though not identified by genetic overlap, are discovered by functional overlap. This disease network portraits rheumatoid arthritis, asthma, atherosclerosis, pulmonary diseases and Crohn’s disease as hubs and thus pointing to common inflammatory processes underlying disease pathophysiology. We identify several described associations such as the inverse comorbidity relationship between Alzheimer’s disease and neoplasms. Furthermore, we investigate the disruptions in protein interactions by mapping mutations onto the domains involved in the interaction, suggesting hypotheses on the causal link between diseases. Finally, we provide several proof-of-principle examples in which we model the effect of the mutation and the change of the association strength, which could explain the observed comorbidity between diseases caused by the same genetic alterations.
format	article
author	Carlota Rubio-Perez Emre Guney Daniel Aguilar Janet Piñero Javier Garcia-Garcia Barbara Iadarola Ferran Sanz Narcís Fernandez-Fuentes Laura I. Furlong Baldo Oliva
author_facet	Carlota Rubio-Perez Emre Guney Daniel Aguilar Janet Piñero Javier Garcia-Garcia Barbara Iadarola Ferran Sanz Narcís Fernandez-Fuentes Laura I. Furlong Baldo Oliva
author_sort	Carlota Rubio-Perez
title	Genetic and functional characterization of disease associations explains comorbidity
title_short	Genetic and functional characterization of disease associations explains comorbidity
title_full	Genetic and functional characterization of disease associations explains comorbidity
title_fullStr	Genetic and functional characterization of disease associations explains comorbidity
title_full_unstemmed	Genetic and functional characterization of disease associations explains comorbidity
title_sort	genetic and functional characterization of disease associations explains comorbidity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/38eab5823fb84a85925a9c46a44f2ef9
work_keys_str_mv	AT carlotarubioperez geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity AT emreguney geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity AT danielaguilar geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity AT janetpinero geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity AT javiergarciagarcia geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity AT barbaraiadarola geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity AT ferransanz geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity AT narcisfernandezfuentes geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity AT lauraifurlong geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity AT baldooliva geneticandfunctionalcharacterizationofdiseaseassociationsexplainscomorbidity
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Genetic and functional characterization of disease associations explains comorbidity

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