Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis

Venous thromboembolism is a complex disease with a high heritability. There are significant associations among Factor XI (FXI) levels and SNPs in the KNG1 and F11 loci. Our aim was to identify the genetic variation of KNG1 and F11 that might account for the variability of FXI levels. The KNG1 and F1...

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Autores: Martin-Fernandez, Laura|||0000-0002-8909-508X, Gavidia-Bovadilla, Giovana, Corrales Insa, Irene|||0000-0002-0647-0340, Brunel, Helena|||0000-0002-1036-7928, Ramírez, Lorena, López, Sonia|||0000-0002-5023-5153, Souto, Juan Carlos|||0000-0003-2092-5142, Vidal, Francisco|||0000-0001-8089-4945, Soria Fernández, José Manuel|||0000-0002-6226-4293
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:253874
Acceso en línea:https://ddd.uab.cat/record/253874
https://dx.doi.org/urn:doi:10.1371/journal.pone.0176301
Access Level:acceso abierto
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spelling Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosisMartin-Fernandez, Laura|||0000-0002-8909-508XGavidia-Bovadilla, GiovanaCorrales Insa, Irene|||0000-0002-0647-0340Brunel, Helena|||0000-0002-1036-7928Ramírez, LorenaLópez, Sonia|||0000-0002-5023-5153Souto, Juan Carlos|||0000-0003-2092-5142Vidal, Francisco|||0000-0001-8089-4945Soria Fernández, José Manuel|||0000-0002-6226-4293Venous thromboembolism is a complex disease with a high heritability. There are significant associations among Factor XI (FXI) levels and SNPs in the KNG1 and F11 loci. Our aim was to identify the genetic variation of KNG1 and F11 that might account for the variability of FXI levels. The KNG1 and F11 loci were sequenced completely in 110 unrelated individuals from the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project using Next Generation Sequencing on an Illumina MiSeq. The GAIT-2 Project is a study of 935 individuals in 35 extended Spanish families selected through a proband with idiopathic thrombophilia. Among the 110 individuals, a subset of 40 individuals was chosen as a discovery sample for identifying variants. A total of 762 genetic variants were detected. Several significant associations were established among common variants and low-frequency variants sets in KNG1 and F11 with FXI levels using the PLINK and SKAT packages. Among these associations, those of rs710446 and five low-frequency variant sets in KNG1 with FXI level variation were significant after multiple testing correction and permutation. Also, two putative pathogenic mutations related to high and low FXI levels were identified by data filtering and in silico predictions. This study of KNG1 and F11 loci should help to understand the connection between genotypic variation and variation in FXI levels. The functional genetic variants should be useful as markers of thromboembolic risk.Universitat Autònoma de Barcelona 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/253874https://dx.doi.org/urn:doi:10.1371/journal.pone.0176301reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI-11/0184Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI-12/01494Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI-15/00269Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0042/0032Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0042/0053Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 FI12/00322open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2538742026-06-06T12:50:31Z
dc.title.none.fl_str_mv Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis
title Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis
spellingShingle Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis
Martin-Fernandez, Laura|||0000-0002-8909-508X
title_short Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis
title_full Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis
title_fullStr Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis
title_full_unstemmed Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis
title_sort Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis
dc.creator.none.fl_str_mv Martin-Fernandez, Laura|||0000-0002-8909-508X
Gavidia-Bovadilla, Giovana
Corrales Insa, Irene|||0000-0002-0647-0340
Brunel, Helena|||0000-0002-1036-7928
Ramírez, Lorena
López, Sonia|||0000-0002-5023-5153
Souto, Juan Carlos|||0000-0003-2092-5142
Vidal, Francisco|||0000-0001-8089-4945
Soria Fernández, José Manuel|||0000-0002-6226-4293
author Martin-Fernandez, Laura|||0000-0002-8909-508X
author_facet Martin-Fernandez, Laura|||0000-0002-8909-508X
Gavidia-Bovadilla, Giovana
Corrales Insa, Irene|||0000-0002-0647-0340
Brunel, Helena|||0000-0002-1036-7928
Ramírez, Lorena
López, Sonia|||0000-0002-5023-5153
Souto, Juan Carlos|||0000-0003-2092-5142
Vidal, Francisco|||0000-0001-8089-4945
Soria Fernández, José Manuel|||0000-0002-6226-4293
author_role author
author2 Gavidia-Bovadilla, Giovana
Corrales Insa, Irene|||0000-0002-0647-0340
Brunel, Helena|||0000-0002-1036-7928
Ramírez, Lorena
López, Sonia|||0000-0002-5023-5153
Souto, Juan Carlos|||0000-0003-2092-5142
Vidal, Francisco|||0000-0001-8089-4945
Soria Fernández, José Manuel|||0000-0002-6226-4293
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
description Venous thromboembolism is a complex disease with a high heritability. There are significant associations among Factor XI (FXI) levels and SNPs in the KNG1 and F11 loci. Our aim was to identify the genetic variation of KNG1 and F11 that might account for the variability of FXI levels. The KNG1 and F11 loci were sequenced completely in 110 unrelated individuals from the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project using Next Generation Sequencing on an Illumina MiSeq. The GAIT-2 Project is a study of 935 individuals in 35 extended Spanish families selected through a proband with idiopathic thrombophilia. Among the 110 individuals, a subset of 40 individuals was chosen as a discovery sample for identifying variants. A total of 762 genetic variants were detected. Several significant associations were established among common variants and low-frequency variants sets in KNG1 and F11 with FXI levels using the PLINK and SKAT packages. Among these associations, those of rs710446 and five low-frequency variant sets in KNG1 with FXI level variation were significant after multiple testing correction and permutation. Also, two putative pathogenic mutations related to high and low FXI levels were identified by data filtering and in silico predictions. This study of KNG1 and F11 loci should help to understand the connection between genotypic variation and variation in FXI levels. The functional genetic variants should be useful as markers of thromboembolic risk.
publishDate 2017
dc.date.none.fl_str_mv 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv 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://ddd.uab.cat/record/253874
https://dx.doi.org/urn:doi:10.1371/journal.pone.0176301
url https://ddd.uab.cat/record/253874
https://dx.doi.org/urn:doi:10.1371/journal.pone.0176301
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI-11/0184
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI-12/01494
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI-15/00269
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0042/0032
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD12/0042/0053
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 FI12/00322
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
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
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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