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

Zimo Sha; Tianzhichao Hou; Taojie Zhou; Yang Dai; Yangyang Bao; Qi Jin; Jing Ye; Yiming Lu; Liqun Wu

doi:10.3389/fcvm.2023.1093255

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

Front Cardiovasc Med. 2023 Feb 15:10:1093255. doi: 10.3389/fcvm.2023.1093255. eCollection 2023.

Authors

Zimo Sha¹, Tianzhichao Hou², Taojie Zhou¹, Yang Dai^{1

3}, Yangyang Bao¹, Qi Jin¹, Jing Ye^{4

5}, Yiming Lu^{4

5}, Liqun Wu¹

Affiliations

¹ Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Geriatrics, Medical Center on Aging of Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁵ International Laboratory in Hematology and Cancer, Shanghai Jiao Tong University School of Medicine/Ruijin Hospital/CNRS/Inserm/Côte d'Azur University, Shanghai, China.

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.

Keywords: atrial fibrillation; bidirectional Mendelian randomization (MR); expression quantitative trait loci (eQTL); genome-wide association study; leukocyte telomere length; protein quantitative trait loci (pQTL).