A型血等位基因与15种心血管代谢疾病的累加关联：一项英国生物银行生命历程研究

Additive association of blood group A allele with 15 cardiometabolic diseases: a UK Biobank life-course study.

作者信息

Zhao Ran, Xian Wenyan, Ma Yihao, Napolioni Valerio, Lau Patrick W C, Tian Xiao-Li, Le Guen Yann, Franke Andre, Huang Jie

机构信息

School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.

College of Letters & Science, University of California, Berkeley, CA, USA.

出版信息

Cardiovasc Diabetol. 2025 Mar 10;24(1):113. doi: 10.1186/s12933-025-02669-w.

DOI:10.1186/s12933-025-02669-w

PMID:40065387

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11895148/

Abstract

BACKGROUND

Although existing studies have reported associations between blood group A and cardiometabolic diseases (CMD), most have focused on dominant inheritance models. However, genome-wide association studies have mostly been based on additive genotypes. This study aims to investigate the association between the blood group A allele and 15 CMD using recessive, dominant, and additive models and identify potential mediators.

METHODS

This study leveraged data from over 320,000 participants with O and A blood groups in the UK Biobank to investigate the association between blood group A allele and 15 major CMD under recessive, dominant, and gene dosage (additive) models. Protein data from nearly 30,000 participants were used to analyze the association between ABO protein levels and CMD. Mediation analysis further explored whether blood cell count traits and blood biochemistry mediate the association between the number of A allele and CMD.

RESULTS

The additive model demonstrates a dose-response association of the blood group A allele with venous thromboembolism (VTE), myocardial infarction (MI), ischemic stroke (IS), type 2 diabetes mellitus (T2DM), and heart failure (HF), among others. Each additional A allele increased disease risk, particularly for VTE (HR = 1.273, P[FDR] = 4.43 × 10). ABO protein levels also correlated with five CMD outcomes, particularly VTE and coronary artery disease (CAD). Mediation analyses revealed that blood cell traits (e.g., hemoglobin, hematocrit) and biochemistries (e.g., aspartate aminotransferase to alanine aminotransferase ratio, apolipoprotein B) significantly mediated the associations for specific CMD, suggesting shared biological mechanisms.

CONCLUSIONS

Our findings reveal that blood group A allele is associated with an increased risk of multiple CMD, particularly under the additive model. Some blood cell count traits and blood biochemistries play significant mediating roles.

摘要

背景

尽管现有研究已报道了A型血与心血管代谢疾病（CMD）之间的关联，但大多数研究集中在显性遗传模型上。然而，全基因组关联研究大多基于加性基因型。本研究旨在使用隐性、显性和加性模型研究A型血等位基因与15种CMD之间的关联，并确定潜在的中介因素。

方法

本研究利用英国生物银行中超过320,000名O型和A型血参与者的数据，在隐性、显性和基因剂量（加性）模型下研究A型血等位基因与15种主要CMD之间的关联。使用近30,000名参与者的蛋白质数据来分析ABO蛋白水平与CMD之间的关联。中介分析进一步探讨血细胞计数特征和血液生化指标是否介导A型血等位基因数量与CMD之间的关联。

结果

加性模型显示A型血等位基因与静脉血栓栓塞（VTE）、心肌梗死（MI）、缺血性中风（IS）、2型糖尿病（T2DM）和心力衰竭（HF）等存在剂量反应关联。每增加一个A型血等位基因都会增加疾病风险，尤其是VTE（风险比=1.273，经错误发现率校正的P值=4.43×10）。ABO蛋白水平也与5种CMD结局相关，尤其是VTE和冠状动脉疾病（CAD）。中介分析表明，血细胞特征（如血红蛋白、血细胞比容）和生化指标（如天冬氨酸转氨酶与丙氨酸转氨酶比值、载脂蛋白B）显著介导了特定CMD的关联，提示存在共同的生物学机制。