Evidence-Based Medicine
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Dec 26, 2023; 11(36): 8475-8485
Published online Dec 26, 2023. doi: 10.12998/wjcc.v11.i36.8475
Mendelian randomization provides evidence for a causal effect of serum insulin-like growth factor family concentration on risk of atrial fibrillation
Sha Lin, Jie Tang, Xing Li, Gang Wu, Yi-Fei Lin, Yi-Fei Li
Sha Lin, Jie Tang, Xing Li, Gang Wu, Yi-Fei Li, Department of Pediatrics and Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Yi-Fei Lin, Yi-Fei Li, Medical Device Regulatory Research and Evaluation Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Co-corresponding authors: Yi-Fei Li and Gang Wu.
Author contributions: Lin S, Tang J and Li X collected the data; Lin S performed the MR analysis; Wu G, Lin YF and Li YF conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content; Wu G, Lin YF and Li YF were responsible for the revision of the manuscript for important intellectual content; all authors issued final approval for the version to be submitted.
Conflict-of-interest statement: All the authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yi-Fei Li, MD, Professor, Department of Pediatrics and Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital, Sichuan University, No. 20 3rd Section, South Renmin Road, Chengdu 610041, Sichuan Province, China. liyfwcsh@scu.edu.cn
Received: October 1, 2023
Peer-review started: October 1, 2023
First decision: November 16, 2023
Revised: November 10, 2023
Accepted: December 7, 2023
Article in press: December 7, 2023
Published online: December 26, 2023
Processing time: 81 Days and 17.4 Hours
Abstract
BACKGROUND

Atrial fibrillation (AF) is one of the most common persistent arrhythmias among adult cardiovascular diseases. It is important to identify potential risk factors for AF. Members of the insulin-like growth factor (IGF) family exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases, and previous population-based studies indicate associations between IGF family members and AF. However, the causal effects of IGF family members in AF have not been evaluated.

AIM

In the current study two-sample Mendelian Randomization (MR) was used to assess genetic relationships between IGF family members and AF.

METHODS

MR was performed based on genome-wide association study (GWAS) datasets, and concentration levels of 14 IGF family members were retrieved. An initial MR analysis was conducted to identify single nucleotide polymorphisms potentially associated with IGF serum concentrations. A GWAS meta-analysis including 60620 AF cases and 970216 control participants of European ancestry was then conducted to identify AF causal effects. Two-sample MR packages were used to perform MR analysis in R. MR-Egger, weighted median (WM), and inverse variance weighted (IVW) methods were used.

RESULTS

In two-sample MR assessments there were lower levels of circulating IGF binding protein 3 in both WM [odds ratio (OR) 0.964, 95% confidence interval (CI) 0.940–0.960, P = 0.006] and IVW (OR 0.968, 95%CI: 0.947–0.987, P = 0.001) analyses. Higher serum levels of IGF2 receptor were associated with AF (OR 1.045, 95%CI: 1.016–1.076, P = 0.039). In reverse MR analysis conducted to investigate casual effects, elevated levels of circulating CYR61 were associated with AF (OR 1.060, 95%CI: 1.005–1.119, P = 0.031).

CONCLUSION

The results of the present study provide novel insights into the pathogenesis of AF, and the implications of serum IGF family member concentrations when assessing the risk of AF. The study generated evidence on the potential roles of developmental pathological effects in the pathogenesis of AF. Further observational and experimental studies are critically needed.

Keywords: Atrial fibrillation; Genome-wide association study; Insulin-like growth factor binding protein 3; Insulin-like growth factor family; Mendelian randomization

Core Tip: Due to the high prevalence of atrial fibrillation (AF), and adverse outcomes related to it, it is important to identify risk factors associated with development of the condition. Insulin-like growth factor (IGF) family members exert a variety of effects on various cell types in the context of the pathogenesis of cardiovascular diseases, and previous population-based studies indicate associations between IGF family members and AF. However, the causal effects of IGF family members in AF have not been evaluated. The results of the current study provide novel insights on the pathogenesis of AF, and implications of serum IGF family member concentrations when assessing the risk of AF. The study generated evidence on the potential roles of developmental pathological effects in the pathogenesis of AF. Further observational and experimental studies are critically needed.