Dataset Information

Causal relationship between atrial fibrillation and leukocyte telomere length: A two sample, bidirectional Mendelian randomization study.

ABSTRACT:

Background

Atrial fibrillation (AF) is an age-related disease, while telomeres play a central role in aging. But the relationship between AF and telomere length (LTL) is still controversial. This study aims to examine the potential causal association between AF and LTL by using Mendelian randomization (MR).

Methods

Bidirectional two-sample MR, expression and protein quantitative trait loci (eQTL and pQTL)-based MR were performed using genetic variants from United Kingdom Biobank, FinnGen, and a meta-analysis study, which comprised nearly 1 million participants in the Atrial Fibrillation Study and 470,000 participants in the Telomere Length Study. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, complementary analysis approaches and sensitivity analysis were applied.

Results

The forward MR revealed a significant causal estimate for the genetically predicted AF with LTL shortening [IVW: odds ratio (OR) = 0.989, p = 0.007; eQTL-IVW: OR = 0.988, p = 0.005; pQTL-IVW: OR = 0.975, p < 0.005]. But in the reverse MR analysis, genetically predicted LTL has no significant correlation with AF (IVW: OR = 0.995, p = 0.916; eQTL-IVW: OR = 0.999, p = 0.995; pQTL-IVW: OR = 1.055, p = 0.570). The FinnGen replication data yielded similar findings. Sensitivity analysis ensured the stability of the results.

Conclusion

The presence of AF leads to LTL shortening rather than the other way around. Aggressive intervention for AF may delay the telomere attrition.

SUBMITTER: Sha Z

PROVIDER: S-EPMC9975167 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Causal relationship between atrial fibrillation and leukocyte telomere length: A two sample, bidirectional Mendelian randomization study.

Sha Zimo Z Hou Tianzhichao T Zhou Taojie T Dai Yang Y Bao Yangyang Y Jin Qi Q Ye Jing J Lu Yiming Y Wu Liqun L

Frontiers in cardiovascular medicine 20230215

<h4>Background</h4>Atrial fibrillation (AF) is an age-related disease, while telomeres play a central role in aging. But the relationship between AF and telomere length (LTL) is still controversial. This study aims to examine the potential causal association between AF and LTL by using Mendelian randomization (MR).<h4>Methods</h4>Bidirectional two-sample MR, expression and protein quantitative trait loci (eQTL and pQTL)-based MR were performed using genetic variants from United Kingdom Biobank, ...[more]

PMID: 36873417

Similar Datasets

Project description:Background: Observational studies have identified impaired lung function accessed by forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or the ratio of FEV1 over FVC (FEV1/FVC) as an independent risk factor for atrial fibrillation (AF). However, the result may be affected by confounders or reverse causality. Methods: We performed univariable MR (uvMR), multivariable MR (mvMR) and bidirectional two-sample MR to jointly estimate the causality of lung function with AF. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, three complementary sensitive analyses approaches including MR-Egger regression, weighted median (WM) MR and Pleiotropy Residual Sum and Outlier (MR-PRESSO) in uvMR as well as mvMR-Egger and mvMR-PRESSO in mvMR were applied to control for pleiotropy. Linkage disequilibrium score (LDSC) regression was applied to estimate genetic correlation between lung function and AF. Results: All forward and reverse uvMR analyses consistently suggested absent causal relations between lung function and AF risk [forward IVW: odds ratio (OR)FEV1 = 1.031, 95% CI = 0.909-1.169, P = 0.630; ORFVC = 1.002, 95% CI = 0.834-1.204, P = 0.982; ORFEV1/FVC = 1.076, 95% CI = 0.966-1.199, P = 0.182; reverse IVW: ORFEV1 = 0.986, 95% CI = 0.966-1.007, P = 0.187; ORFVC = 0.985, 95% CI = 0.965-1.006, P = 0.158; ORFEV1/FVC = 0.994, 95% CI = 0.973-1.015, P = 0.545]. The forward MR-Egger showed that each standard deviation (SD) increase in FEV1/FVC was related to a higher AF risk (OR = 1.502, 95% CI = 1.178-1.915, P = 0.006) without heterogeneity (Q_pval = 0.064), but pleiotropy effect exist (intercept = -0.017, P = 0.012). However, this significant effect disappeared after adjustment of FEV1 and FVC (OR = 1.523, 95% CI = 0.445-5.217, P = 0.503) in mvMR. No evidence was found for independent causal effects of FEV1 and FVC on AF in mvMR analysis by using mvIVW method (ORFEV1 = 0.501, 95% CI = 0.056-4.457, P = 0.496; ORFVC = 1.969, 95% CI = 0.288-13.474, P = 0.490). Notably, the association between lung function and AF were replicated using the FinnGen cohort data. Conclusions: Our findings reported no coheritability between lung function and AF, and failed to find substantial causal relation between decreased lung function and risk of AF. However, lung function and AF were both associated with inflammation, which may be potential pathway, warranting further study.

Project description:BackgroundTelomere length is closely linked to the aging phenotype, where cellular aging results in the production of a cascade of cell factors and the senescence-associated secretory phenotype (SASP), leading to an inflammatory response. The presence of inflammation plays a crucial role in the formation of intracranial aneurysms. Nevertheless, the relationship between telomere length and intracranial aneurysms remains unclear. This study aims to explore the causal connection between telomere length and intracranial aneurysms through the utilization of Mendelian randomization (MR) analysis.MethodsData on telomere length were obtained from the genome-wide association studies conducted on the UK Biobank, comprising a total of 472,174 participants. Data on intracranial aneurysms were obtained from the summary dataset of the Global Genome-wide Association Study (GWAS) conducted by the International Stroke Genetics Consortium. The dataset consisted of 7,495 cases and 71,934 controls, all of European descent. Initially, the linkage disequilibrium score was used to investigate the connection between telomere length and intracranial aneurysms. Subsequently, a bidirectional MR was conducted using two-sample analysis to assess whether there is a causal connection between telomere length and intracranial aneurysm risk. The results were analyzed utilizing five MR methods, with the inverse variance weighted method serving as the main methodology. In addition, we did various analyses to evaluate the presence of heterogeneity, pleiotropy, and sensitivity in the study results. A reverse MR analysis was conducted to investigate potential reverse causal links.ResultsIn the forward MR analysis, it was observed that both the inverse variance-weighted and weighted median analyses implied a potential causal relationship between longer telomere length and a decreased incidence of intracranial aneurysms (IVW: OR = 0.66, 95% CI: 0.47-0.92, p = 1.49 × 10-2). There was no heterogeneity or horizontal pleiotropy. The findings were verified to be robust through the utilization of leave-one-out analysis. The use of reverse MR analysis did not establish a potential causal link between the occurrence of intracranial aneurysms and telomere length.ConclusionThere may exist a potential correlation between longer telomere length and a decreased likelihood of intracranial aneurysms within the European population. The present study offers novel insights into the correlation between telomere length and intracranial aneurysms. Additional research is required to clarify the underlying mechanisms and validate our discoveries in diverse populations.

Dataset Information

Causal relationship between atrial fibrillation and leukocyte telomere length: A two sample, bidirectional Mendelian randomization study.

Background

Methods

Results

Conclusion

Publications

Causal relationship between atrial fibrillation and leukocyte telomere length: A two sample, bidirectional Mendelian randomization study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets