Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample : The CHRIS Study
| Autor: | Marzia De Bortoli, Nikola Dordevic, David B. Emmert, Vladimir Vukovic, Luisa Foco, Deborah Mascalzoni, Francisco S. Domingues, Johannes Rainer, Rupert Paulmichl, Peter P. Pramstaller, Alessandra Rossini, Vinicius Veri Hernandes, Christian X. Weichenberger, Cristian Pattaro, Chiara Losi, Claudia B. Volpato, Martin Gögele, Christian Fuchsberger, Yuri D’Elia, Giulia Pontali |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Population
Genome-wide association study Single-nucleotide polymorphism Biology Biochemistry Microbiology Polymorphism Single Nucleotide Article symbols.namesake Genotype Humans GWAS Cooperative Health Research in South Tyrol Genetic Predisposition to Disease atrial fibrillation rare alleles Cardiac and Cardiovascular Systems Allele education Molecular Biology Gene Medicinsk genetik Genetics Sanger sequencing education.field_of_study Kardiologi Family aggregation Middle Aged metabolomics QR1-502 familial aggregation symbols Medical Genetics Genome-Wide Association Study |
| Zdroj: | Biomolecules Volume 11 Issue 11 Biomolecules, Vol 11, Iss 1663, p 1663 (2021) |
| Popis: | 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 (p-value < 5 × 10−8) around SNPs rs745582874, next to gene PBX1, and rs768476991, within gene PCCA, 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 (p-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|