Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study

Atrial fibrillation (AF) is a supraventricular arrhythmia deriving from uncoordinated electrical activation with considerable associated morbidity and mortality. To expand the limited understanding of AF biological mechanisms, we performed two screenings, investigating the genetic and metabolic dete...

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Autores principales:	David B. Emmert, Vladimir Vukovic, Nikola Dordevic, Christian X. Weichenberger, Chiara Losi, Yuri D’Elia, Claudia Volpato, Vinicius V. Hernandes, Martin Gögele, Luisa Foco, Giulia Pontali, Deborah Mascalzoni, Francisco S. Domingues, Rupert Paulmichl, Peter P. Pramstaller, Cristian Pattaro, Alessandra Rossini, Johannes Rainer, Christian Fuchsberger, Marzia De Bortoli
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	atrial fibrillation GWAS rare alleles familial aggregation metabolomics Cooperative Health Research in South Tyrol Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/af4026a9c15446038e6a8b5fd793952a
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spelling	oai:doaj.org-article:af4026a9c15446038e6a8b5fd793952a2021-11-25T16:53:31ZGenetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study10.3390/biom111116632218-273Xhttps://doaj.org/article/af4026a9c15446038e6a8b5fd793952a2021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1663https://doaj.org/toc/2218-273XAtrial fibrillation (AF) is a supraventricular arrhythmia deriving from uncoordinated electrical activation with considerable associated morbidity and mortality. To expand the limited understanding of AF biological mechanisms, we performed two screenings, investigating the genetic and metabolic determinants of AF in the Cooperative Health Research in South Tyrol study. We found 110 AF cases out of 10,509 general population individuals. A genome-wide association scan (GWAS) identified two novel loci (<em>p</em>-value < 5 × 10<sup>−8</sup>) around SNPs rs745582874, next to gene <em>PBX1</em>, and rs768476991, within gene <em>PCCA</em>, with genotype calling confirmed by Sanger sequencing. Risk alleles at both SNPs were enriched in a family detected through familial aggregation analysis of the phenotype, and both rare alleles co-segregated with AF. The metabolic screening of 175 metabolites, in a subset of individuals, revealed a 41% lower concentration of lysophosphatidylcholine lysoPC a C20:3 in AF cases compared to controls (<em>p</em>-adj = 0.005). The genetic findings, combined with previous evidence, indicate that the two identified GWAS loci may be considered novel genetic rare determinants for AF. Considering additionally the association of lysoPC a C20:3 with AF by metabolic screening, our results demonstrate the valuable contribution of the combined genomic and metabolomic approach in studying AF in large-scale population studies.David B. EmmertVladimir VukovicNikola DordevicChristian X. WeichenbergerChiara LosiYuri D’EliaClaudia VolpatoVinicius V. HernandesMartin GögeleLuisa FocoGiulia PontaliDeborah MascalzoniFrancisco S. DominguesRupert PaulmichlPeter P. PramstallerCristian PattaroAlessandra RossiniJohannes RainerChristian FuchsbergerMarzia De BortoliMDPI AGarticleatrial fibrillationGWASrare allelesfamilial aggregationmetabolomicsCooperative Health Research in South TyrolMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1663, p 1663 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	atrial fibrillation GWAS rare alleles familial aggregation metabolomics Cooperative Health Research in South Tyrol Microbiology QR1-502
spellingShingle	atrial fibrillation GWAS rare alleles familial aggregation metabolomics Cooperative Health Research in South Tyrol Microbiology QR1-502 David B. Emmert Vladimir Vukovic Nikola Dordevic Christian X. Weichenberger Chiara Losi Yuri D’Elia Claudia Volpato Vinicius V. Hernandes Martin Gögele Luisa Foco Giulia Pontali Deborah Mascalzoni Francisco S. Domingues Rupert Paulmichl Peter P. Pramstaller Cristian Pattaro Alessandra Rossini Johannes Rainer Christian Fuchsberger Marzia De Bortoli Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study
description	Atrial fibrillation (AF) is a supraventricular arrhythmia deriving from uncoordinated electrical activation with considerable associated morbidity and mortality. To expand the limited understanding of AF biological mechanisms, we performed two screenings, investigating the genetic and metabolic determinants of AF in the Cooperative Health Research in South Tyrol study. We found 110 AF cases out of 10,509 general population individuals. A genome-wide association scan (GWAS) identified two novel loci (<em>p</em>-value < 5 × 10<sup>−8</sup>) around SNPs rs745582874, next to gene <em>PBX1</em>, and rs768476991, within gene <em>PCCA</em>, with genotype calling confirmed by Sanger sequencing. Risk alleles at both SNPs were enriched in a family detected through familial aggregation analysis of the phenotype, and both rare alleles co-segregated with AF. The metabolic screening of 175 metabolites, in a subset of individuals, revealed a 41% lower concentration of lysophosphatidylcholine lysoPC a C20:3 in AF cases compared to controls (<em>p</em>-adj = 0.005). The genetic findings, combined with previous evidence, indicate that the two identified GWAS loci may be considered novel genetic rare determinants for AF. Considering additionally the association of lysoPC a C20:3 with AF by metabolic screening, our results demonstrate the valuable contribution of the combined genomic and metabolomic approach in studying AF in large-scale population studies.
format	article
author	David B. Emmert Vladimir Vukovic Nikola Dordevic Christian X. Weichenberger Chiara Losi Yuri D’Elia Claudia Volpato Vinicius V. Hernandes Martin Gögele Luisa Foco Giulia Pontali Deborah Mascalzoni Francisco S. Domingues Rupert Paulmichl Peter P. Pramstaller Cristian Pattaro Alessandra Rossini Johannes Rainer Christian Fuchsberger Marzia De Bortoli
author_facet	David B. Emmert Vladimir Vukovic Nikola Dordevic Christian X. Weichenberger Chiara Losi Yuri D’Elia Claudia Volpato Vinicius V. Hernandes Martin Gögele Luisa Foco Giulia Pontali Deborah Mascalzoni Francisco S. Domingues Rupert Paulmichl Peter P. Pramstaller Cristian Pattaro Alessandra Rossini Johannes Rainer Christian Fuchsberger Marzia De Bortoli
author_sort	David B. Emmert
title	Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study
title_short	Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study
title_full	Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study
title_fullStr	Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study
title_full_unstemmed	Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study
title_sort	genetic and metabolic determinants of atrial fibrillation in a general population sample: the chris study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/af4026a9c15446038e6a8b5fd793952a
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Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study

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