Mendelian randomization study reveals a causal relationship between serum iron status and coronary heart disease and related cardiovascular diseases

Fenglan Liu; Yanfei Liu; Shihan Xu; Qing Wang; Fengqin Xu; Yue Liu

doi:10.3389/fcvm.2023.1152201

Mendelian randomization study reveals a causal relationship between serum iron status and coronary heart disease and related cardiovascular diseases

Front Cardiovasc Med. 2023 Jun 13:10:1152201. doi: 10.3389/fcvm.2023.1152201. eCollection 2023.

Authors

Fenglan Liu^#^{1

2

3}, Yanfei Liu^#^{1

2}, Shihan Xu^{1

2}, Qing Wang^{1

2}, Fengqin Xu^{1

2}, Yue Liu²

Affiliations

¹ The Second Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
² National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
³ School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou, China.

^# Contributed equally.

Abstract

Background: Growing observational studies have shown that abnormal systemic iron status is associated with Coronary heart disease (CHD). However, these results from observational studies was not entirely consistent.It remains unclear whether this relationship represents causality.It is necessary to explore the causal relationship between iron status and CHD and related cardiovascular diseases (CVD).

Objective: We aimed to investigate the potential casual relationship between serum iron status and CHD and related CVD using a two-sample Mendelian randomization (MR) approach.

Methods: Genetic statistics for single nucleotide polymorphisms (SNPs) between four iron status parameters were identified in a large-scale genome-wide association study (GWAS) conducted by the Iron Status Genetics organization. Three independent single nucleotide polymorphisms (SNPs) (rs1800562, rs1799945, and rs855791) aligned with four iron status biomarkers were used as instrumental variables. CHD and related CVD genetic statistics We used publicly available summary-level GWAS data. Five different MR methods random effects inverse variance weighting (IVW), MR Egger, weighted median, weighted mode, and Wald ratio were used to explore the causal relationship between serum iron status and CHD and related CVD.

Results: In the MR analysis, we found that the causal effect of serum iron (OR = 0.995, 95% CI = 0.992-0.998, p = 0.002) was negatively associated with the odds of coronary atherosclerosis (AS). Transferrin saturation (TS) (OR = 0.885, 95% CI = 0.797-0.982, p = 0.02) was negatively associated with the odds of Myocardial infarction (MI).

Conclusion: This MR analysis provides evidence for a causal relationship between whole-body iron status and CHD development. Our study suggests that a high iron status may be associated with a reduced risk of developing CHD.

Keywords: Mendelian randomization; cardiovascular disease; causal effect; genome-wide association studies; iron status.

Grants and funding

This study is supported by The Young Qihuang Scholar of the “Tens of Millions” Talent Project of China, the key project of scientific and technological innovation project sponsored by Chinese Academy of Chinese Medical Sciences (CI2021A01406), and the Special Project for Outstanding Young Talents of China Academy of Chinese Medical Sciences (ZZ15-YQ-017 and ZZ13-YQ-001-A1).