Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria
James A Watson, Stije J Leopold, Julie A Simpson, Nicholas PJ Day, Arjen M Dondorp, Nicholas J White
ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2019
Case fatality rates in severe falciparum malaria depend on the pattern and degree of vital organ dysfunction. Recent large-scale case-control analyses of pooled severe malaria data reported that glucose-6-phosphate dehydrogenase deficiency (G6PDd) was protective against cerebral malaria but increased the risk of severe malarial anaemia. A novel formulation of the balancing selection hypothesis was proposed as an explanation for these findings, whereby the selective advantage is driven by the competing risks of death from cerebral malaria and death from severe malarial anaemia. We re-analysed these claims using causal diagrams and showed that they are subject to collider bias. A simulation ba..View full abstract
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Awarded by National Health and Medical Research Council
Wellcome Trust James A Watson Nicholas PJ Day Arjen M DondorpNational Health and Medical Research Council Senior Research Fellowship 1104975 Julie A SimpsonThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.