rs8176719

mixedMag 6.5

This is a frameshift variant variant in the ABO gene.

Key Literature Trait Associations

Venous thromboembolism

Carrying the G (non-O) allele at rs8176719 consistently elevates risk of venous thromboembolism (VTE) across multiple large studies and meta-analyses. The largest meta-analysis (38 studies, 10,305 cases) found a pooled OR of 2.09 for non-O vs O blood group. A UK Biobank analysis (n=406,755) found up to OR 1.56 for thromboembolic events in non-O groups. A Swedish population cohort found HR 1.30 per G allele copy. The ABO locus accounts for approximately 17–21% of population-attributable VTE risk and is considered the most common genetic risk factor for VTE, operating primarily through elevated VWF and Factor VIII levels in non-O individuals.

Dentali F et al. “Non-O blood type is the commonest genetic risk factor for VTE: results from a meta-analysis of the literature.” Seminars in Thrombosis and Hemostasis (2012)

Allele G

OR 2.09

p —

Meta-analysis

multi-ancestry

Groot HE et al. “Genetically Determined ABO Blood Group and its Associations With Health and Disease.” Arteriosclerosis, Thrombosis, and Vascular Biology (2020)

Allele G

OR 1.56

p —

N 406,755

Preliminary work

European (UK Biobank)

Manderstedt E et al. “Thrombotic risk determined by ABO, F8, and VWF variants in a population-based cohort study.” Research and Practice in Thrombosis and Haemostasis (2025)

Allele G

OR —

p —

N 28,794

Preliminary work

Swedish

Wu O et al. “ABO(H) blood groups and vascular disease: a systematic review and meta-analysis.” Journal of Thrombosis and Haemostasis : Jth (2008)

Allele G

OR 1.79

p —

Meta-analysis

multi-ancestry

ABO Blood Group (O vs Non-O)

This single-base deletion at codon 261 of the ABO gene shifts the reading frame, abolishing glycosyltransferase activity and producing blood type O. Non-O blood groups (A, B, AB) carry higher circulating levels of von Willebrand factor (vWF) and Factor VIII, because ABO glycans on vWF reduce its clearance rate. People with blood type O have approximately half the risk of venous thromboembolism compared to those with non-O blood types (OR ~0.52). ABO genotype accounts for ~20-25% of variation in vWF levels.

Groot HE et al. “Genetically Determined ABO Blood Group and its Associations With Health and Disease.” Arteriosclerosis, Thrombosis, and Vascular Biology (2020)

Allele C

OR —

p —

N 406,755

Preliminary work

European (UK Biobank)

Heit JA et al. “A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q.” Journal of Thrombosis and Haemostasis : Jth 10(8):1521-1531 (2012)

Allele C

OR 1.92

p 2.4e-16

Large GWAS

Malaria

Blood group O (deletion allele at rs8176719) is one of the most strongly replicated protective factors against severe Plasmodium falciparum malaria. A landmark GWAS in over 11,000 African children confirmed blood group O as one of the strongest genome-wide signals for severe malaria resistance. Mechanistically, group O red cells resist P. falciparum rosetting (clumping of infected and uninfected erythrocytes), a process that promotes microvascular obstruction. A Ghanaian cohort study found 45% reduced odds of placental malaria in group O primiparae. Non-O individuals carrying the G allele thus face elevated susceptibility to severe and complicated malaria in endemic regions.

Band G et al. “A novel locus of resistance to severe malaria in a region of ancient balancing selection.” Nature (2015)

Allele G

OR —

p 9.5e-11

N 25,000

Large GWAS

African (multi-site)

Bedu-Addo G et al. “Reduced prevalence of placental malaria in primiparae with blood group O.” Malaria Journal (2014)

Allele G

OR 0.55

p 7.0e-3

N 839

Preliminary work

Ghanaian

Pancreatic cancer

Non-O blood groups (G allele at rs8176719) are consistently associated with elevated pancreatic cancer risk across multiple independent studies. A genome-wide association study first identified the ABO locus (rs505922 in LD with rs8176719) as the leading common susceptibility locus for pancreatic cancer with OR ~1.20. A consortium analysis of 12 prospective cohorts (1,534 cases, 1,583 controls) found type A had OR 1.38, type B OR 1.53, and type AB OR 1.47 versus type O. Blood group O has a population-attributable fraction of approximately 19.5% for pancreatic cancer. The mechanism may involve ABO antigens expressed on pancreatic ductal cells modulating tumor microenvironment or immune recognition.

Wolpin BM et al. “Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium.” Cancer Research (2010)

Allele G

OR 1.53

p —

N 3,117

Major Consortium Study

multi-ancestry (12 international cohorts)

Amundadottir L et al. “Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.” Nature Genetics 41(9):986-90 (2009)

Allele G

OR 1.20

p 5.4e-8

N 8,946

Small GWAS

European

Coronary heart disease

Non-O blood groups (G allele at rs8176719) are associated with modestly elevated coronary heart disease (CHD) risk, primarily mediated through elevated VWF, Factor VIII, and LDL cholesterol levels in non-O individuals. A systematic review and meta-analysis of 17 studies (225,810 participants) found blood group O was protective (OR 0.85, 95% CI 0.78–0.94) while blood group A carried elevated risk (OR 1.14). An earlier meta-analysis confirmed non-O groups had OR 1.25 for myocardial infarction. These effects are modest relative to the VTE association, reflecting the predominance of thrombotic over atherosclerotic pathways.

Chen Z et al. “ABO blood group system and the coronary artery disease: an updated systematic review and meta-analysis.” Scientific Reports (2016)

Allele G

OR 0.85

p 8.0e-4

N 225,810

Meta-analysis

multi-ancestry

Wu O et al. “ABO(H) blood groups and vascular disease: a systematic review and meta-analysis.” Journal of Thrombosis and Haemostasis : Jth (2008)

Allele G

OR 1.25

p —

Meta-analysis

multi-ancestry

Ischemic stroke

Non-O blood groups (G allele) are associated with elevated ischemic stroke risk, primarily through VWF-mediated thrombotic and cardioembolic mechanisms. A large meta-analysis of 72 studies (145,499 cases, 2,113,736 controls) found non-O blood groups carried OR 1.13 (95% CI 1.07–1.21) for ischemic stroke, with blood group A showing OR 1.19 and AB showing OR 1.24. An earlier meta-analysis (2014) also found OR 1.17 for non-O versus O. The association is consistent but of smaller magnitude than the VTE association, likely reflecting the diversity of stroke etiologies.

Lilova Z et al. “Blood group and ischemic stroke, myocardial infarction, and peripheral vascular disease: A meta-analysis of over 145,000 cases and 2,000,000 controls.” Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association (2023)

Allele G

OR 1.13

p 1.0e-3

N 2,259,235

Meta-analysis

multi-ancestry

Dentali F et al. “ABO blood group and vascular disease: an update.” Seminars in Thrombosis and Hemostasis (2014)

Allele G

OR 1.17

p 3.0e-2

Candidate gene study

multi-ancestry

Heparin-induced thrombocytopenia

Counterintuitively, the deletion (O-group) allele at rs8176719 — not the G allele — increases risk of heparin-induced thrombocytopenia (HIT). A GWAS of 4,166 participants confirmed that blood group O individuals have OR 1.42 (95% CI 1.26–1.61, p=3.09×10⁻⁸) for HIT functional assay positivity, with the rs8176719 C insertion (non-O) being protective. This may reflect differences in platelet factor 4 (PF4) interactions with ABO antigens. Blood group O patients receiving heparin are at modestly elevated HIT risk compared to non-O patients.

Karnes JH et al. “ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia.” Blood (2022)

Allele G

OR 1.42

p 3.1e-8

N 4,952

Large GWAS

European

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GWAS Catalog Trait Associations (18)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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Research that mentions this SNP (2)

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Myocardial infarction, prothrombotic genotypes, and venous thrombosis risk: The Tromsø Study

AssociationN=2,402Joakim K. Sejrup et al.(2020)· Research and Practice in Thrombosis and Haemostasis

Prospective case-cohort study examining whether 5 prothrombotic SNPs explain the increased venous thromboembolism (VTE) risk after myocardial infarction (MI). Patients with MI had a 1.4-fold increased VTE risk (HR 1.44, 95% CI 1.07-1.96), but adjustment for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11) did not attenuate this relationship (adjusted HR 1.52). Individual SNPs associated with VTE in non-MI subjects (F5 HR 2.20, ABO HR 1.44), but their combination with MI did not yield excess VTE risk.

Traits studied:Deep vein thrombosisPulmonary embolismVenous thromboembolism

PubMed DOI Metascience Observatory

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A Genome‐Wide Association Study for Venous Thromboembolism: The Extended Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

AssociationN=11,615Weihong Tang et al.(2013)· Genetic Epidemiology

A large genome-wide association study of venous thromboembolism (VTE) in 9 European ancestry cohorts (4,849 cases total) identified genome-wide significant associations at F5, ABO, F11, and FGG loci. The FGG locus (rs6536024, RR=0.80, p<5.0×10⁻¹³) and F11 locus (rs4253399, RR=1.24, p<5.0×10⁻¹³) showed novel associations with reduced and increased VTE risk respectively. Additional borderline associations (p<5.0×10⁻⁶) were identified near SUSD1 and OTUD7A, representing new candidate genes for VTE.

rs8176719

Key Literature Trait Associations

Venous thromboembolism

ABO Blood Group (O vs Non-O)

Malaria

Pancreatic cancer

Coronary heart disease

Ischemic stroke

Heparin-induced thrombocytopenia

GWAS Catalog Trait Associations (18)

Research that mentions this SNP (2)

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