The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes

Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phen...

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Detalles Bibliográficos
Autores: Brunel, Helena, Massanet, Raimon, Martinez Perez, Angel, Ziyatdinov, Andrey, Martin-Fernandez, Laura, Souto, Juan Carlos, Perera Lluna, Alexandre|||0000-0001-6427-851X, Soria, José Manuel
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/102293
Acceso en línea:https://hdl.handle.net/2117/102293
https://dx.doi.org/10.1371/journal.pone.0167187
Access Level:acceso abierto
Palabra clave:Genomics
Genòmica
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
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spelling The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypesBrunel, HelenaMassanet, RaimonMartinez Perez, AngelZiyatdinov, AndreyMartin-Fernandez, LauraSouto, Juan CarlosPerera Lluna, Alexandre|||0000-0001-6427-851XSoria, José ManuelGenomicsGenòmicaÀrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::BioinformàticaTraditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process. First, we define new phenotypic meta-variables (linear combinations of the original phenotypes), named metaphenotypes, by applying Independent Component Analysis for the multivariate analysis of correlated phenotypes (i.e. the levels of coagulation pathway–related proteins). The resulting metaphenotypes integrate the information regarding the underlying biological process (i.e. thrombus/clot formation). Secondly, we take advantage of a family based Genome Wide Association Study to identify genetic elements influencing these metaphenotypes and consequently thrombosis risk. Our study utilized data from the GAIT Project (Genetic Analysis of Idiopathic Thrombophilia). We obtained 15 metaphenotypes, which showed significant heritabilities, ranging from 0.2 to 0.7. These results indicate the importance of genetic factors in the variability of these traits. We found 4 metaphenotypes that showed significant associations with SNPs. The most relevant were those mapped in a region near the HRG, FETUB and KNG1 genes. Our results are provocative since they show that the KNG1 locus plays a central role as a genetic determinant of the entire coagulation pathway and thrombus/clot formation. Integrating data from multiple correlated measurements through metaphenotypes is a promising approach to elucidate the hidden genetic mechanisms underlying complex diseases.20162016-12-2220172017-03-10journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/102293https://dx.doi.org/10.1371/journal.pone.016718728005926reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/1022932026-05-27T15:37:01Z
dc.title.none.fl_str_mv The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes
title The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes
spellingShingle The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes
Brunel, Helena
Genomics
Genòmica
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
title_short The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes
title_full The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes
title_fullStr The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes
title_full_unstemmed The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes
title_sort The Central role of KNG1 gene as a genetic determinant of coagulation pathway-related traits: Exploring metaphenotypes
dc.creator.none.fl_str_mv Brunel, Helena
Massanet, Raimon
Martinez Perez, Angel
Ziyatdinov, Andrey
Martin-Fernandez, Laura
Souto, Juan Carlos
Perera Lluna, Alexandre|||0000-0001-6427-851X
Soria, José Manuel
author Brunel, Helena
author_facet Brunel, Helena
Massanet, Raimon
Martinez Perez, Angel
Ziyatdinov, Andrey
Martin-Fernandez, Laura
Souto, Juan Carlos
Perera Lluna, Alexandre|||0000-0001-6427-851X
Soria, José Manuel
author_role author
author2 Massanet, Raimon
Martinez Perez, Angel
Ziyatdinov, Andrey
Martin-Fernandez, Laura
Souto, Juan Carlos
Perera Lluna, Alexandre|||0000-0001-6427-851X
Soria, José Manuel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Genomics
Genòmica
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
topic Genomics
Genòmica
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
description Traditional genetic studies of single traits may be unable to detect the pleiotropic effects involved in complex diseases. To detect the correlation that exists between several phenotypes involved in the same biological process, we introduce an original methodology to analyze sets of correlated phenotypes involved in the coagulation cascade in genome-wide association studies. The methodology consists of a two-stage process. First, we define new phenotypic meta-variables (linear combinations of the original phenotypes), named metaphenotypes, by applying Independent Component Analysis for the multivariate analysis of correlated phenotypes (i.e. the levels of coagulation pathway–related proteins). The resulting metaphenotypes integrate the information regarding the underlying biological process (i.e. thrombus/clot formation). Secondly, we take advantage of a family based Genome Wide Association Study to identify genetic elements influencing these metaphenotypes and consequently thrombosis risk. Our study utilized data from the GAIT Project (Genetic Analysis of Idiopathic Thrombophilia). We obtained 15 metaphenotypes, which showed significant heritabilities, ranging from 0.2 to 0.7. These results indicate the importance of genetic factors in the variability of these traits. We found 4 metaphenotypes that showed significant associations with SNPs. The most relevant were those mapped in a region near the HRG, FETUB and KNG1 genes. Our results are provocative since they show that the KNG1 locus plays a central role as a genetic determinant of the entire coagulation pathway and thrombus/clot formation. Integrating data from multiple correlated measurements through metaphenotypes is a promising approach to elucidate the hidden genetic mechanisms underlying complex diseases.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-12-22
2017
2017-03-10
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/102293
https://dx.doi.org/10.1371/journal.pone.0167187
28005926
url https://hdl.handle.net/2117/102293
https://dx.doi.org/10.1371/journal.pone.0167187
identifier_str_mv 28005926
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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