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Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria

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 increase...

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Autores principales: Watson, James A, Leopold, Stije J, Simpson, Julie A, Day, Nicholas PJ, Dondorp, Arjen M, White, Nicholas J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361583/
https://www.ncbi.nlm.nih.gov/pubmed/30688212
http://dx.doi.org/10.7554/eLife.43154
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author Watson, James A
Leopold, Stije J
Simpson, Julie A
Day, Nicholas PJ
Dondorp, Arjen M
White, Nicholas J
author_facet Watson, James A
Leopold, Stije J
Simpson, Julie A
Day, Nicholas PJ
Dondorp, Arjen M
White, Nicholas J
author_sort Watson, James A
collection PubMed
description 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 based sensitivity analysis, varying the strength of the known effect of G6PDd on anaemia, showed that this bias is sufficient to explain all of the observed association. Future genetic epidemiology studies in severe malaria would benefit from the use of causal reasoning.
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spelling pubmed-63615832019-02-06 Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria Watson, James A Leopold, Stije J Simpson, Julie A Day, Nicholas PJ Dondorp, Arjen M White, Nicholas J eLife Epidemiology and Global Health 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 based sensitivity analysis, varying the strength of the known effect of G6PDd on anaemia, showed that this bias is sufficient to explain all of the observed association. Future genetic epidemiology studies in severe malaria would benefit from the use of causal reasoning. eLife Sciences Publications, Ltd 2019-01-28 /pmc/articles/PMC6361583/ /pubmed/30688212 http://dx.doi.org/10.7554/eLife.43154 Text en © 2019, Watson et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Epidemiology and Global Health
Watson, James A
Leopold, Stije J
Simpson, Julie A
Day, Nicholas PJ
Dondorp, Arjen M
White, Nicholas J
Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria
title Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria
title_full Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria
title_fullStr Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria
title_full_unstemmed Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria
title_short Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria
title_sort collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria
topic Epidemiology and Global Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361583/
https://www.ncbi.nlm.nih.gov/pubmed/30688212
http://dx.doi.org/10.7554/eLife.43154
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