The Interplay Between Titin, Polygenic Risk, and Modifiable Cardiovascular Risk Factors in Atrial Fibrillation.
Atrial Fibrillation
/ complications
Cardiomyopathy, Dilated
/ etiology
Connectin
/ genetics
Diabetes Mellitus
/ epidemiology
Effect Modifier, Epidemiologic
Female
Genetic Variation
Humans
Hypertension
/ epidemiology
Male
Middle Aged
Multifactorial Inheritance
Obesity
/ epidemiology
Preventive Health Services
Proportional Hazards Models
Risk Assessment
/ methods
Smoking
/ epidemiology
United Kingdom
/ epidemiology
Exome Sequencing
/ methods
Journal
The Canadian journal of cardiology
ISSN: 1916-7075
Titre abrégé: Can J Cardiol
Pays: England
ID NLM: 8510280
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
23
06
2020
revised:
03
12
2020
accepted:
06
12
2020
pubmed:
30
12
2020
medline:
25
11
2021
entrez:
29
12
2020
Statut:
ppublish
Résumé
Common and rare variants, including those in the gene for the cardiac structural protein titin (TTN), have been implicated in the risk of developing atrial fibrillation (AF). However, the effect of genetic variants on risk of AF compared with established modifiable risk factors is unclear. The objective of this study was to evaluate the risk of AF and associated cardiovascular complications in TTN variant carriers and examine interactions between TTN variants or common variants and modifiable AF risk factors. We used whole exome sequencing data of 49,881 individuals and genotyping data of 408,572 individuals from the UK Biobank to examine the associations of TTN variants, polygenic risk, and 4 risk factors (hypertension, diabetes, obesity, and smoking) with AF. Adjusted hazard ratios (aHRs) were calculated with the use of Cox proportional hazards models. TTN variant carrier status was associated with a higher risk of AF (aHR 2.10, 95% CI 1.59-2.79; P = 2.54 × 10 Genetic and modifiable cardiovascular risk factors contribute to the probability of developing AF. Our findings highlight the potential utility of incorporating data from targeted sequencing or genotyping of common variants to further inform AF risk stratification and aggressive management of modifiable cardiovascular risk factors.
Sections du résumé
BACKGROUND
Common and rare variants, including those in the gene for the cardiac structural protein titin (TTN), have been implicated in the risk of developing atrial fibrillation (AF). However, the effect of genetic variants on risk of AF compared with established modifiable risk factors is unclear. The objective of this study was to evaluate the risk of AF and associated cardiovascular complications in TTN variant carriers and examine interactions between TTN variants or common variants and modifiable AF risk factors.
METHODS
We used whole exome sequencing data of 49,881 individuals and genotyping data of 408,572 individuals from the UK Biobank to examine the associations of TTN variants, polygenic risk, and 4 risk factors (hypertension, diabetes, obesity, and smoking) with AF. Adjusted hazard ratios (aHRs) were calculated with the use of Cox proportional hazards models.
RESULTS
TTN variant carrier status was associated with a higher risk of AF (aHR 2.10, 95% CI 1.59-2.79; P = 2.54 × 10
CONCLUSIONS
Genetic and modifiable cardiovascular risk factors contribute to the probability of developing AF. Our findings highlight the potential utility of incorporating data from targeted sequencing or genotyping of common variants to further inform AF risk stratification and aggressive management of modifiable cardiovascular risk factors.
Identifiants
pubmed: 33373724
pii: S0828-282X(20)31195-8
doi: 10.1016/j.cjca.2020.12.024
pii:
doi:
Substances chimiques
Connectin
0
TTN protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
848-856Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.