Population-specific ABO haplotypes reveal distinct venous thromboembolism risk in East Asians: insights from a large-scale genetic study
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background The ABO blood group locus is a well-established genetic determinant of venous thromboembolism (VTE) risk in both individuals of European and East Asian ancestry. Recent studies have identified key ABO haplotypes tagged by four common SNPs—rs2519093 (A1), rs1053878 (A2), rs8176743 (B), and rs8176719/rs41302905 (O1/O2)—that influence both incident and recurrent VTE risk in Europeans. However, marked differences in ABO allele frequencies and haplotype structures across ancestries may render European findings inapplicable to East Asians, highlighting a critical gap in understanding the genetic basis of VTE in this population. Methods We conducted a haplotype-based association study using ABO-tagging SNPs (including rs512770 that distinguishes between O1.1 and O1.2) in 1576 VTE cases from China Pulmonary Thromboembolism Registry Study (CURES) and 17,535 ancestry-matched controls, adjusted for age, sex, and genetic principal components to evaluate the effects of ABO haplotypes on VTE risk and recurrence. Findings Our analyses revealed key population-specific differences: in East Asians, the rs1053878-A allele is consistently co-inherited with the rs2519093-T allele, precluding its use as a specific marker for the A2 blood group, unlike in Europeans. Furthermore, all non-O1 haplotypes were homogeneously associated with a ∼1.4-fold increased risk of VTE ( p = 5.2 × 10 −20 ) and a ∼1.7-fold increased risk of recurrence ( p = 0.023), compared to the O1.1 group. Notably, the O1.2 blood group was also associated with a 1.7-fold increased risk of recurrence ( p = 0.039). Interpretation These findings highlight fundamental differences in ABO haplotype structure and disease associations between East Asians and Europeans. Our study provides a population-specific SNP panel—rs8176719, rs2519093, rs1053878, rs8176743, and rs512770—for accurate genetic risk assessment of VTE in East Asians, underscoring the importance of ancestry-tailored approaches to thrombotic disease prediction. Funding This study is funded by the Chinese Academy of Medical Science Innovation Fund for Medical Sciences (No. 2024-I2M-TS-035, No. 2021-I2M-1-061), National Key Research and Development Program of China (No. 2024YFE0101900, No. 2023YFC2507200), National Natural Science Foundation of China (No. 82470046, No. 82241029) and Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2024ZD0528700).
Authors: Haobo Li, Zhu Zhang, Hong Chen, Yuanhua Yang, Jun Wan, Xiaomao Xu, Yingqun Ji, Guoru Yang, Ping Zhang, Jing Han, Kejing Ying, Qixia Xu, Ling Zhu, Tao Yang, Yingyun Fu, Haoyi Weng, Dingyi Wang, Yunxia Zhang, Shuai Zhang, Qiang Huang, Wanmu Xie, Xianbo Zuo, Qin Luo, David-Alexandre Trégouët, Zhenguo Zhai, Chen Wang
Institutions: Université de Bordeaux, Inserm, Chinese Academy of Medical Sciences & Peking Union Medical College, China-Japan Friendship Hospital, Bordeaux Population Health, The Affiliated Yongchuan Hospital of Chongqing Medical University, Capital Medical University, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Anzhen Hospital, Beijing Hospital, Tongji University, Shanghai East Hospital, Weifang People's Hospital, Dongguan People’s Hospital, Guizhou Provincial People's Hospital, Sir Run Run Shaw Hospital, Zhejiang University, University of Science and Technology of China, Shandong Provincial Hospital, Jinan University, ShenZhen People’s Hospital, Central South University, Xinjiang Medical University, Second Affiliated Hospital of Xinjiang Medical University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,250
OpenAlex ID: W7116797555