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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MDPI AG
2021-11-01
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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 |
collection | DOAJ |
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. |
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spelling | doaj.art-af4026a9c15446038e6a8b5fd793952a2023-11-22T22:34:31ZengMDPI AGBiomolecules2218-273X2021-11-011111166310.3390/biom11111663Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS StudyDavid B. Emmert0Vladimir Vukovic1Nikola Dordevic2Christian X. Weichenberger3Chiara Losi4Yuri D’Elia5Claudia Volpato6Vinicius V. Hernandes7Martin Gögele8Luisa Foco9Giulia Pontali10Deborah Mascalzoni11Francisco S. Domingues12Rupert Paulmichl13Peter P. Pramstaller14Cristian Pattaro15Alessandra Rossini16Johannes Rainer17Christian Fuchsberger18Marzia De Bortoli19Eurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyDepartment of Cardiology, Tappeiner F. Merano Hospital, 39012 Merano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyDepartment of Cardiology, Tappeiner F. Merano Hospital, 39012 Merano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyEurac Research, Institute for Biomedicine (Affiliated to the University of Lübeck), 39100 Bolzano, ItalyAtrial 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.https://www.mdpi.com/2218-273X/11/11/1663atrial fibrillationGWASrare allelesfamilial aggregationmetabolomicsCooperative Health Research in South Tyrol |
spellingShingle | 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 Biomolecules atrial fibrillation GWAS rare alleles familial aggregation metabolomics Cooperative Health Research in South Tyrol |
title | 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_short | 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 |
topic | atrial fibrillation GWAS rare alleles familial aggregation metabolomics Cooperative Health Research in South Tyrol |
url | https://www.mdpi.com/2218-273X/11/11/1663 |
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