Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation
Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation
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DOI：
10.1182/blood.2020008997
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发表时间：
2021-04-29
期刊：
影响因子：
20.3
通讯作者：
Morange, Pierre-Emmanuel
中科院分区：
文献类型：
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作者：
Goumidi, Louisa;Thibord, Florian;Morange, Pierre-Emmanuel
遗传风险评分（GRS）分析是复杂疾病个体风险预测模型的常用方法。在静脉血栓形成（VT）中，这种类型的分析需要整合ABO血型位点的信息，这是主要的易感位点之一。然而，在正确评估ABO位点与VT风险之间的关系时，哪些单核苷酸多态性（snp）必须进行研究，目前尚无共识。通过对来自6项研究的5425例病例和8445例对照的ABO血型标记snp的综合单倍型分析，我们证明仅使用rs8176719（标记为O1）来正确评估ABO位点对VT风险的影响是不理想的，因为5%的rs8176719- delg携带者不会增加发生VT的风险。相反，我们建议使用4个snp， rs2519093（标记为A1）， rs1053878 (A2), rs8176743 (B)和rs41302905 （O2）。在评估abolocus对VT风险的影响时，避免任何风险误估。与O1单倍型相比，A2单倍型与VT风险适度增加相关（优势比，类似于1.2），A1和B单倍型与风险增加类似于1.8倍相关，而O2单倍型倾向于轻微保护（优势比，类似于0.80）。此外，尽管A1和B血型与血管性血变因子和VIII因子血浆水平升高相关，但只有A1血型与ICAM水平相关，但方向相反，这为充分了解ABO基因位点介导的心血管性状生物学效应谱留下了额外的探索途径。
Genetic risk score (GRS) analysis is a popular approach to derive individual risk prediction models for complex diseases. In venous thrombosis (VT), such type of analysis shall integrate information at the ABO blood group locus, which is one of the major susceptibility loci. However, there is no consensus about which single nucleotide polymorphisms (SNPs) must be investigated when properly assessing association between ABO locus and VT risk. Using comprehensive haplotype analyses of ABO blood group tagging SNPs in 5425 cases and 8445 controls from 6 studies, we demonstrate that using only rs8176719 (tagging O1) to correctly assess the impact of ABO locus on VT risk is suboptimal, because 5% of rs8176719-delG carriers do not have an increased risk of developing VT. Instead, we recommend the use of 4 SNPs, rs2519093 (tagging A1), rs1053878 (A2), rs8176743 (B), and rs41302905 (O2), when assessing the impact ofABOlocus on VT risk to avoid any risk misestimation. Compared with the O1 haplotype, the A2 haplotype is associated with a modest increase in VT risk (odds ratio, similar to 1.2), the A1 and B haplotypes are associated with an similar to 1.8-fold increased risk, whereas the O2 haplotype tends to be slightly protective (odds ratio, similar to 0.80). In addition, although the A1 and B blood groups are associated with increased von Willebrand factor and factor VIII plasma levels, only the A1 blood group is associated with ICAM levels, but in an opposite direction, leaving additional avenues to be explored to fully understand the spectrum of biological effects mediated by ABO locus on cardiovascular traits.