Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants

Genome-wide association studies (GWASs) are instrumental in identifying loci harboring common single-nucleotide variants (SNVs) that affect human traits and diseases. GWAS hits emerge in clusters, but the focus is often on the most significant hit in each trait- or disease-associated locus. The rema...

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Autores: Pinsach Abuin, Mel·lina, Olmo, Bernat del, Pérez Agustín, Adrian, Matés Ramírez, Jesús, Allegue Toscano, Catarina, Iglesias, Anna, Ma, Qi, Merkurjev, Daria, Konovalov, Sergiy, Zhang, Jing, Sheikh, Farah, Telenti, Amalio, Brugada Terradellas, Josep, Brugada, Ramon, Gymrek, Melissa, Di Iulio, Julia, Garcia-Bassets, Ivan, Pagans i Lista, Sara
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/19629
Acceso en línea:http://hdl.handle.net/10256/19629
Access Level:acceso abierto
Palabra clave:Mort sobtada
Arrítmia
Sudden death
Arrhythmia
Brugada, Síndrome de
Brugada syndrome
Cor -- Malalties -- Aspectes genètics
Heart -- Diseases -- Genetic aspects
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repository_id_str
spelling Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variantsPinsach Abuin, Mel·linaOlmo, Bernat delPérez Agustín, AdrianMatés Ramírez, JesúsAllegue Toscano, CatarinaIglesias, AnnaMa, QiMerkurjev, DariaKonovalov, SergiyZhang, JingSheikh, FarahTelenti, AmalioBrugada Terradellas, JosepBrugada, RamonGymrek, MelissaDi Iulio, JuliaGarcia-Bassets, IvanPagans i Lista, SaraMort sobtadaArrítmiaSudden deathArrhythmiaBrugada, Síndrome deBrugada syndromeCor -- Malalties -- Aspectes genèticsHeart -- Diseases -- Genetic aspectsGenome-wide association studies (GWASs) are instrumental in identifying loci harboring common single-nucleotide variants (SNVs) that affect human traits and diseases. GWAS hits emerge in clusters, but the focus is often on the most significant hit in each trait- or disease-associated locus. The remaining hits represent SNVs in linkage disequilibrium (LD) and are considered redundant and thus frequently marginally reported or exploited. Here, we interrogate the value of integrating the full set of GWAS hits in a locus repeatedly associated with cardiac conduction traits and arrhythmia, SCN5A-SCN10A. Our analysis reveals 5 common 7-SNV haplotypes (Hap1-5) with 2 combinations associated with life-threatening arrhythmia-Brugada syndrome (the risk Hap1/1 and protective Hap2/3 genotypes). Hap1 and Hap2 share 3 SNVs; thus, this analysis suggests that assuming redundancy among clustered GWAS hits can lead to confounding disease-risk associations and supports the need to deconstruct GWAS data in the context of haplotype compositionElsevier2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/19629http://hdl.handle.net/10256/19629Cell Reports Medicine, 2021, vol. 2, núm. 4, p. 100250Articles publicats (D-CM)Pinsach Abuin, Mel·lina Olmo, Bernat del Pérez Agustín, Adrian Matés Ramírez, Jesús Allegue Toscano, Catarina Iglesias, Anna Ma, Qi Merkurjev, Daria Konovalov, Sergiy Zhang, Jing Sheikh, Farah Telenti, Amalio Brugada Terradellas, Josep Brugada, Ramon Gymrek, Melissa Di Iulio, Julia Garcia Bassets, Ivan Pagans i Lista, Sara 2021 Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants Cell Reports Medicine 2 4 100250reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.xcrm.2021.100250info:eu-repo/semantics/altIdentifier/issn/2666-3791Reconeixement 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessoai:recercat.cat:10256/196292026-05-29T05:05:01Z
dc.title.none.fl_str_mv Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants
title Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants
spellingShingle Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants
Pinsach Abuin, Mel·lina
Mort sobtada
Arrítmia
Sudden death
Arrhythmia
Brugada, Síndrome de
Brugada syndrome
Cor -- Malalties -- Aspectes genètics
Heart -- Diseases -- Genetic aspects
title_short Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants
title_full Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants
title_fullStr Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants
title_full_unstemmed Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants
title_sort Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants
dc.creator.none.fl_str_mv Pinsach Abuin, Mel·lina
Olmo, Bernat del
Pérez Agustín, Adrian
Matés Ramírez, Jesús
Allegue Toscano, Catarina
Iglesias, Anna
Ma, Qi
Merkurjev, Daria
Konovalov, Sergiy
Zhang, Jing
Sheikh, Farah
Telenti, Amalio
Brugada Terradellas, Josep
Brugada, Ramon
Gymrek, Melissa
Di Iulio, Julia
Garcia-Bassets, Ivan
Pagans i Lista, Sara
author Pinsach Abuin, Mel·lina
author_facet Pinsach Abuin, Mel·lina
Olmo, Bernat del
Pérez Agustín, Adrian
Matés Ramírez, Jesús
Allegue Toscano, Catarina
Iglesias, Anna
Ma, Qi
Merkurjev, Daria
Konovalov, Sergiy
Zhang, Jing
Sheikh, Farah
Telenti, Amalio
Brugada Terradellas, Josep
Brugada, Ramon
Gymrek, Melissa
Di Iulio, Julia
Garcia-Bassets, Ivan
Pagans i Lista, Sara
author_role author
author2 Olmo, Bernat del
Pérez Agustín, Adrian
Matés Ramírez, Jesús
Allegue Toscano, Catarina
Iglesias, Anna
Ma, Qi
Merkurjev, Daria
Konovalov, Sergiy
Zhang, Jing
Sheikh, Farah
Telenti, Amalio
Brugada Terradellas, Josep
Brugada, Ramon
Gymrek, Melissa
Di Iulio, Julia
Garcia-Bassets, Ivan
Pagans i Lista, Sara
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mort sobtada
Arrítmia
Sudden death
Arrhythmia
Brugada, Síndrome de
Brugada syndrome
Cor -- Malalties -- Aspectes genètics
Heart -- Diseases -- Genetic aspects
topic Mort sobtada
Arrítmia
Sudden death
Arrhythmia
Brugada, Síndrome de
Brugada syndrome
Cor -- Malalties -- Aspectes genètics
Heart -- Diseases -- Genetic aspects
description Genome-wide association studies (GWASs) are instrumental in identifying loci harboring common single-nucleotide variants (SNVs) that affect human traits and diseases. GWAS hits emerge in clusters, but the focus is often on the most significant hit in each trait- or disease-associated locus. The remaining hits represent SNVs in linkage disequilibrium (LD) and are considered redundant and thus frequently marginally reported or exploited. Here, we interrogate the value of integrating the full set of GWAS hits in a locus repeatedly associated with cardiac conduction traits and arrhythmia, SCN5A-SCN10A. Our analysis reveals 5 common 7-SNV haplotypes (Hap1-5) with 2 combinations associated with life-threatening arrhythmia-Brugada syndrome (the risk Hap1/1 and protective Hap2/3 genotypes). Hap1 and Hap2 share 3 SNVs; thus, this analysis suggests that assuming redundancy among clustered GWAS hits can lead to confounding disease-risk associations and supports the need to deconstruct GWAS data in the context of haplotype composition
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/19629
http://hdl.handle.net/10256/19629
url http://hdl.handle.net/10256/19629
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.xcrm.2021.100250
info:eu-repo/semantics/altIdentifier/issn/2666-3791
dc.rights.none.fl_str_mv Reconeixement 4.0 Internacional
http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Reconeixement 4.0 Internacional
http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Cell Reports Medicine, 2021, vol. 2, núm. 4, p. 100250
Articles publicats (D-CM)
Pinsach Abuin, Mel·lina Olmo, Bernat del Pérez Agustín, Adrian Matés Ramírez, Jesús Allegue Toscano, Catarina Iglesias, Anna Ma, Qi Merkurjev, Daria Konovalov, Sergiy Zhang, Jing Sheikh, Farah Telenti, Amalio Brugada Terradellas, Josep Brugada, Ramon Gymrek, Melissa Di Iulio, Julia Garcia Bassets, Ivan Pagans i Lista, Sara 2021 Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants Cell Reports Medicine 2 4 100250
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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