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Whether the non-O blood groups encoded by the specific <jats:italic>ABO<\/jats:italic> genotypes <jats:italic>AO<\/jats:italic>, <jats:italic>BO<\/jats:italic>, <jats:italic>AA<\/jats:italic>, <jats:italic>BB<\/jats:italic> and <jats:italic>AB<\/jats:italic> differ in their associations with severe malaria and rosetting is unknown. The A and B antigens are host RBC receptors for rosetting, hence we hypothesized that the higher levels of A and\/or B antigen on RBCs from <jats:italic>AA<\/jats:italic>, <jats:italic>BB<\/jats:italic> and <jats:italic>AB<\/jats:italic> genotypes compared to <jats:italic>AO\/BO<\/jats:italic> genotypes could lead to larger rosettes, increased microvascular obstruction and higher risk of malaria pathology. We used a case-control study of Kenyan children and <jats:italic>in vitro<\/jats:italic> adhesion assays to test the hypothesis that \u201cdouble dose\u201d non-<jats:italic>O<\/jats:italic> genotypes (<jats:italic>AA<\/jats:italic>, <jats:italic>BB<\/jats:italic>, <jats:italic>AB<\/jats:italic>) are associated with increased risk of severe malaria and larger rosettes than \u201csingle dose\u201d heterozygotes (<jats:italic>AO<\/jats:italic>, <jats:italic>BO<\/jats:italic>). In the case-control study, compared to <jats:italic>OO<\/jats:italic>, the double dose genotypes consistently had higher odds ratios (OR) for severe malaria than single dose genotypes, with <jats:italic>AB<\/jats:italic> (OR 1.93) and <jats:italic>AO<\/jats:italic> (OR 1.27) showing most marked difference (<jats:italic>p<\/jats:italic> = 0.02, Wald test). <jats:italic>In vitro<\/jats:italic> experiments with blood group A-preferring <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> parasites showed that significantly larger rosettes were formed with <jats:italic>AA<\/jats:italic> and <jats:italic>AB<\/jats:italic> host RBCs compared to <jats:italic>OO<\/jats:italic>, whereas <jats:italic>AO<\/jats:italic> and <jats:italic>BO<\/jats:italic> genotypes rosettes were indistinguishable from <jats:italic>OO<\/jats:italic>. Overall, the data show that <jats:italic>ABO<\/jats:italic> genotype influences <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> rosetting and support the hypothesis that double dose non-<jats:italic>O<\/jats:italic> genotypes confer a greater risk of severe malaria than <jats:italic>AO\/BO<\/jats:italic> heterozygosity.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010910","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T17:46:04Z","timestamp":1694713564000},"page":"e1010910","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Non-O ABO blood group genotypes differ in their associations with Plasmodium falciparum rosetting and severe malaria"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-4365","authenticated-orcid":true,"given":"D. 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