Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.
Elife. 2019 Jan 28;8:e43154. doi: 10.7554/eLife.43154.
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.
严重疟疾的病死率取决于重要器官功能障碍的类型和程度。最近对大量严重疟疾数据进行的病例对照分析报告称,葡萄糖-6-磷酸脱氢酶缺乏症(G6PDd)可预防脑型疟疾,但增加了严重疟疾性贫血的风险。提出了一种新的平衡选择假说的解释,认为这种选择优势是由死于脑型疟疾和死于严重疟疾性贫血的竞争风险驱动的。我们使用因果关系图重新分析了这些说法,并表明它们受到了混杂偏倚的影响。基于模拟的敏感性分析,改变了 G6PDd 对贫血的已知影响的强度,表明这种偏差足以解释所有观察到的关联。未来严重疟疾的遗传流行病学研究将受益于因果推理的应用。