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Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual\u2019s level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations.<\/jats:p>","DOI":"10.7554\/elife.15085","type":"journal-article","created":{"date-parts":[[2017,1,9]],"date-time":"2017-01-09T06:00:19Z","timestamp":1483941619000},"source":"Crossref","is-referenced-by-count":76,"title":["Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia"],"prefix":"10.7554","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7249-0289","authenticated-orcid":true,"given":"Geraldine M","family":"Clarke","sequence":"first","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom"},{"name":"MRC Centre for Genomics and Global Health, University of Oxford, Oxford, United 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