| Title: | Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation |
| Journal: | Blood |
| Published: | 29 Apr 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33512453/ |
| DOI: | https://doi.org/10.1182/blood.2020008997 |
| URL: | https://ashpublications.org/blood/article-pdf/137/17/2394/1805977/bloodbld2020008997r1.pdf |
Publication 9676
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Abstract
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 of ABO locus 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, ∼1.2), the A1 and B haplotypes are associated with an ∼1.8-fold increased risk, whereas the O2 haplotype tends to be slightly protective (odds ratio, ∼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.</p>
28 Authors
- Louisa Goumidi
- Florian Thibord
- Kerri L. Wiggins
- Ruifang Li-Gao
- Mickael R. Brown
- Astrid van Hylckama Vlieg
- Joan-Carles Souto
- José-Manuel Soria
- Manal Ibrahim-Kosta
- Noémie Saut
- Delphine Daian
- Robert Olaso
- Philippe Amouyel
- Stéphanie Debette
- Anne Boland
- Pascal Bailly
- Alanna C. Morrison
- Denis O. Mook-Kanamori
- Jean-François Deleuze
- Andrew Johnson
- Paul S. de Vries
- Maria Sabater-Lleal
- Jacques Chiaroni
- Nicholas L. Smith
- Frits R. Rosendaal
- Daniel I. Chasman
- David-Alexandre Trégouët
- Pierre-Emmanuel Morange
1 Application
| Application ID | Title |
|---|---|
| 40713 | The association of genomic variation, exogenous female hormones, and statin therapy with the risk of incident and recurrent arterial and venous thrombosis |
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