Exploring the causality between ankylosing spondylitis and atrial fibrillation: A two-sample Mendelian randomization study

Abstract

Objective: To study whether ankylosing spondylitis (AS) has a causal effect on the risk of atrial fibrillation (AF) using two-sample Mendelian randomization (MR) analysis.Methods: Single nucleotide polymorphisms (SNPs) were selected as independent instrumental variables (IVs) from a GWAS study of AS. Summary data from a large-scale GWAS meta-analysis of AF was utilized as the outcome dataset. Inverse-variance weighted (IVW) model was used for the primary analysis. Multiple sensitivity and heterogeneity tests were conducted to confirm the robustness of the results.Results: In total, 18 SNPs were identified as IVs for MR analysis. Five MR methods consistently found that ankylosing spondylitis was not causally associated with atrial fibrillation (IVW: OR = 0.983 (0.894, 1.080), p = 0.718; MR-Egger: OR = 1.190 (0.973, 1.456), p = 0.109; Simple mode: OR = 0.888 (0.718, 1.098), p = 0.287; Weighted mode: OR = 0.989 (0.854, 1.147), p = 0.890; Weight median: OR = 0.963 (0.852, 1.088), p = 0.545). Leave-one-out analysis supported the stability of MR results. Both the MR-Egger intercept and MR-PRESSO method revealed the absence of horizontal pleiotropy.Conclusion: The two-sample MR analysis did not support a causal relationship between AS and the risk of AF.

Association of ankylosing spondylitis with cardiovascular disease: a bidirectional two-sample mendelian randomization study

“…Finally, AS has been associated with cardiovascular risk factors such as diabetes ( Chen et al, 2014 ; Chou et al, 2014 ), hypertension ( Chen et al, 2014 ; Chou et al, 2014 ), dyslipidemia ( Chen et al, 2014 ; So et al, 2017 ), obesity ( Catapano et al, 2016 ), and metabolic syndrome ( Haroon et al, 2014 ), which interact with AS and affect the occurrence of CVD complications in AS patients. Our MR analysis did not provide evidence for a causal effect of AS on AF, MI, Coronary atherosclerosis, Ischemic stroke, and VHD, which is consistent with previous MR study results ( Chen et al, 2022 ; Mei et al, 2022 ).…”

“…The applicability of MR studies has been demonstrated in the evaluation of diverse causal relationships between behavioral exposures, educational attainment, socioeconomic statuses, and various diseases ( Tillmann et al, 2017 ; Harrison et al, 2020 ). Furthermore, prior MR explorations have scrutinized the causal implications of AS on stroke ( Mei et al, 2022 ) and atrial fibrillation ( Chen et al, 2022 ). Nonetheless, these endeavors have largely focused on specific forms of CVDs.…”

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“…Finally, AS has been associated with cardiovascular risk factors such as diabetes (Chen et al, 2014;Chou et al, 2014), hypertension (Chen et al, 2014;Chou et al, 2014), dyslipidemia (Chen et al, 2014;So et al, 2017), obesity (Catapano et al, 2016), and metabolic syndrome (Haroon et al, 2014), which interact with AS and affect the occurrence of CVD complications in AS patients. Our MR analysis did not provide evidence for a causal effect of AS on AF, MI, Coronary atherosclerosis, Ischemic stroke, and VHD, which is consistent with previous MR study results (Chen et al, 2022;Mei et al, 2022).…”

Lifestyle habits and gastric cancer in an East Asian population: a Mendelian randomization study

“…At the outset of the research design, single nucleotide polymorphisms (SNPs) ( P < 5 × 10 -5 ) that are strongly related with exposure were selected as IVs. We only used independent SNPs with r 2 < 0.01 within a distance of 5,000 kb in order to remove the chain disequilibrium (LD) bias ( 21 ). Therefore, the default parameters of the TwoSampleMR package in R (physical distance threshold, 5,000 kb, r 2 < 0.01) were set for aggregating the data and clipping possible LD genetic variation.…”