{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:16:50Z","timestamp":1792682210613,"version":"4.5.0"},"reference-count":52,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["209265\/Z\/17\/Z"],"award-info":[{"award-number":["209265\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202800\/Z\/16\/Z"],"award-info":[{"award-number":["202800\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["093956\/Z\/10\/C"],"award-info":[{"award-number":["093956\/Z\/10\/C"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC\\UU\\12023\/26"],"award-info":[{"award-number":["MC\\UU\\12023\/26"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT077383\/Z\/05\/Z"],"award-info":[{"award-number":["WT077383\/Z\/05\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0801439"],"award-info":[{"award-number":["G0801439"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["090770\/Z\/09\/Z 204911\/Z\/16\/Z"],"award-info":[{"award-number":["090770\/Z\/09\/Z 204911\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0600718 G0600230 MR\/M006212\/1"],"award-info":[{"award-number":["G0600718 G0600230 MR\/M006212\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203141\/Z\/16\/Z"],"award-info":[{"award-number":["203141\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206194"],"award-info":[{"award-number":["206194"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,6,22]]},"abstract":"<jats:p>Severe falciparum malaria has substantially affected human evolution. Genetic association studies of patients with clinically defined severe malaria and matched population controls have helped characterise human genetic susceptibility to severe malaria, but phenotypic imprecision compromises discovered associations. In areas of high malaria transmission, the diagnosis of severe malaria in young children and, in particular, the distinction from bacterial sepsis are imprecise. We developed a probabilistic diagnostic model of severe malaria using platelet and white count data. Under this model, we re-analysed clinical and genetic data from 2220 Kenyan children with clinically defined severe malaria and 3940 population controls, adjusting for phenotype mis-labelling. Our model, validated by the distribution of sickle trait, estimated that approximately one-third of cases did not have severe malaria. We propose a data-tilting approach for case-control studies with phenotype mis-labelling and show that this reduces false discovery rates and improves statistical power in genome-wide association studies.<\/jats:p>","DOI":"10.7554\/elife.69698","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T20:01:03Z","timestamp":1625515263000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.69698","source":"Crossref","is-referenced-by-count":30,"title":["Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5524-0325","authenticated-orcid":true,"given":"James A","family":"Watson","sequence":"first","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyne M","family":"Ndila","sequence":"first","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Uyoga","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Macharia","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"Nyutu","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shebe","family":"Mohammed","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ngetsa","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neema","family":"Mturi","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Peshu","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Tsofa","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk","family":"Rockett","sequence":"additional","affiliation":[{"name":"The Wellcome Sanger Institute","place":["Cambridge, United Kingdom"]},{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0482-5689","authenticated-orcid":true,"given":"Stije","family":"Leopold","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1869-8307","authenticated-orcid":true,"given":"Hugh","family":"Kingston","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C","family":"George","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-0645","authenticated-orcid":true,"given":"Kathryn","family":"Maitland","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]},{"name":"Institute of Global Health Innovation, Imperial College, London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-1171","authenticated-orcid":true,"given":"Nicholas PJ","family":"Day","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5190-2395","authenticated-orcid":true,"given":"Arjen M","family":"Dondorp","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Bejon","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]},{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4456-2382","authenticated-orcid":true,"given":"Thomas N","family":"Williams","sequence":"additional","affiliation":[{"name":"KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research-Coast","place":["Kilifi, Kenya"]},{"name":"Institute of Global Health Innovation, Imperial College, London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris C","family":"Holmes","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]},{"name":"Department of Statistics, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-1978","authenticated-orcid":true,"given":"Nicholas J","family":"White","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040267","article-title":"Improving case definitions for severe malaria","volume":"4","author":"Anstey","year":"2007","journal-title":"PLOS Medicine"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13480-z","article-title":"Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania","volume":"10","author":"Band","year":"2019","journal-title":"Nature Communications"},{"key":"bib3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040251","article-title":"Defining childhood severe falciparum malaria for intervention studies","volume":"4","author":"Bejon","year":"2007","journal-title":"PLOS Medicine"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1128\/CMR.15.4.564-594.2002","article-title":"Evolutionary and historical aspects of the burden of malaria","volume":"15","author":"Carter","year":"2002","journal-title":"Clinical Microbiology Reviews"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/S0140-6736(05)67176-0","article-title":"Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial","volume":"366","author":"Dondorp","year":"2005","journal-title":"Lancet"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1016\/S0140-6736(10)61924-1","article-title":"Artesunate versus quinine in the treatment of severe falciparum malaria in african children (AQUAMAT): an open-label, randomised trial","volume":"376","author":"Dondorp","year":"2010","journal-title":"The Lancet"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s11634-018-0329-y","article-title":"From here to infinity: sparse finite versus dirichlet process mixtures in model-based clustering","volume":"13","author":"Fr\u00fchwirth-Schnatter","year":"2019","journal-title":"Advances in Data Analysis and Classification"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"686","DOI":"10.4269\/ajtmh.2002.66.686","article-title":"Prognostic value of thrombocytopenia in african children with falciparum malaria","volume":"66","author":"G\u00e9rardin","year":"2002","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-6-51","article-title":"Outcome of life-threatening malaria in african children requiring endotracheal intubation","volume":"6","author":"G\u00e9rardin","year":"2007","journal-title":"Malaria Journal"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/S0140-6736(08)61734-1","article-title":"Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial","volume":"373","author":"Gomes","year":"2009","journal-title":"The Lancet"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12916-015-0324-5","article-title":"The clinical implications of thrombocytopenia in adults with severe falciparum malaria: a retrospective analysis","volume":"13","author":"Hanson","year":"2015","journal-title":"BMC Medicine"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001297","article-title":"Diagnosing severe falciparum malaria in parasitaemic african children: a prospective evaluation of plasma PfHRP2 measurement","volume":"9","author":"Hendriksen","year":"2012","journal-title":"PLOS Medicine"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1056\/NEJM199607113350202","article-title":"A controlled trial of artemether or quinine in vietnamese adults with severe falciparum malaria","volume":"335","author":"Hien","year":"1996","journal-title":"New England Journal of Medicine"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1007\/s00439-020-02142-6","article-title":"Human genetics and malaria resistance","volume":"139","author":"Kariuki","year":"2020","journal-title":"Human Genetics"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1136\/archdischild-2015-309665","article-title":"Retrospective study of imported falciparum malaria in french paediatric intensive care units","volume":"101","author":"Lanneaux","year":"2016","journal-title":"Archives of Disease in Childhood"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.medmal.2019.02.005","article-title":"Management and prevention of imported malaria in children update of the french guidelines","volume":"50","author":"Leblanc","year":"2020","journal-title":"M\u00e9decine Et Maladies Infectieuses"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002858","article-title":"Investigating causal pathways in severe falciparum malaria: a pooled retrospective analysis of clinical studies","volume":"16","author":"Leopold","year":"2019","journal-title":"PLOS Medicine"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"2483","DOI":"10.1056\/NEJMoa1101549","article-title":"Mortality after fluid bolus in african children with severe infection","volume":"364","author":"Maitland","year":"2011","journal-title":"New England Journal of Medicine"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003509","article-title":"Imputation-based meta-analysis of severe malaria in three african populations","volume":"9","author":"Malaria Genomic Epidemiology Network","year":"2013","journal-title":"PLOS Genetics"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1038\/ng.3107","article-title":"Reappraisal of known malaria resistance loci in a large multicenter study","volume":"46","author":"Malaria Genomic Epidemiology Network","year":"2014","journal-title":"Nature Genetics"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam6393","article-title":"Resistance to malaria through structural variation of red blood cell invasion receptors","volume":"356","author":"Malaria Genomic Epidemiology Network","year":"2017","journal-title":"Science"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"e437","DOI":"10.1016\/S2352-3026(15)00152-0","article-title":"Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria and other diseases in children in Kenya: a case-control and a cohort study","volume":"2","author":"MalariaGEN Consortium","year":"2015","journal-title":"The Lancet Haematology"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.15085","article-title":"Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia","volume":"6","author":"MalariaGEN Consortium","year":"2017","journal-title":"eLife"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"e333","DOI":"10.1016\/S2352-3026(18)30107-8","article-title":"Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study","volume":"5","author":"MalariaGEN Consortium","year":"2018","journal-title":"The Lancet Haematology"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.16320.1","article-title":"Haplotype heterogeneity and low linkage disequilibrium reduce reliable prediction of genotypes for the form of \u03b1-thalassaemia using genome-wide microarray data [version 1; peer review: awaiting peer review]","volume":"5","author":"Ndila","year":"2020","journal-title":"Wellcome Open Research"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1214\/13-AOAS655","article-title":"Likelihood reweighting methods to reduce potential bias in noninferiority trials which rely on historical data to make inference","volume":"7","author":"Nie","year":"2013","journal-title":"The Annals of Applied Statistics"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ebiom.2014.10.006","article-title":"Mechanistic studies of the negative epistatic malaria-protective interaction between sickle cell trait and \u03b1+ thalassemia","volume":"1","author":"Opi","year":"2014","journal-title":"EBioMedicine"},{"key":"bib28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180758","article-title":"Severe imported malaria in children in France: A national retrospective study from 1996 to 2005","volume":"12","author":"Pediatric Imported Malaria Study Group for the \u2018Centre National de R\u00e9f\u00e9rence du Paludisme\u2019","year":"2017","journal-title":"PLOS ONE"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-9-97","article-title":"Randomized controlled trial of artesunate or artemether in vietnamese adults with severe falciparum malaria","volume":"9","author":"Phu","year":"2010","journal-title":"Malaria Journal"},{"key":"bib30","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa191","article-title":"Concomitant bacteremia in adults with severe falciparum malaria","volume":"19","author":"Phu","year":"2020","journal-title":"Clinical Infectious Diseases"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000360","article-title":"Reduced neutrophil count in people of african descent is due to a regulatory variant in the duffy antigen receptor for chemokines gene","volume":"5","author":"Reich","year":"2009","journal-title":"PLOS Genetics"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.35832","article-title":"Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure","volume":"7","author":"Rodriguez-Barraquer","year":"2018","journal-title":"eLife"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1111\/j.1365-2141.2009.07771.x","article-title":"An observational study of children with sickle cell disease in Kilifi, Kenya","volume":"146","author":"Sadarangani","year":"2009","journal-title":"British Journal of Haematology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1016\/S0140-6736(11)60888-X","article-title":"Relation between falciparum malaria and bacteraemia in kenyan children: a population-based, case-control study and a longitudinal study","volume":"378","author":"Scott","year":"2011","journal-title":"The Lancet"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23699","article-title":"Evidence from a natural experiment that malaria parasitemia is pathogenic in retinopathy-negative cerebral malaria","volume":"6","author":"Small","year":"2017","journal-title":"eLife"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"2345","DOI":"10.1002\/sim.4780132206","article-title":"Attributable fraction estimates and case definitions for malaria in endemic Areas","volume":"13","author":"Smith","year":"1994","journal-title":"Statistics in Medicine"},{"key":"bib37","article-title":"RStan: the R interface to Stan","author":"Stan Development Team","year":"2020","unstructured":"Stan Development Team. 2020. RStan: the R interface to Stan. R package version. https:\/\/cran.r-project.org\/web\/packages\/rstan\/vignettes\/rstan.html."},{"key":"bib38","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1111\/1467-9868.00346","article-title":"A direct approach to false discovery rates","volume":"64","author":"Storey","year":"2002","journal-title":"Journal of the Royal Statistical Society: Series B"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nm986","article-title":"Differentiating the pathologies of cerebral malaria by postmortem parasite counts","volume":"10","author":"Taylor","year":"2004","journal-title":"Nature Medicine"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/S1473-3099(12)70055-5","article-title":"Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis","volume":"12","author":"Taylor","year":"2012","journal-title":"The Lancet Infectious Diseases"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/nrg2731","article-title":"Methodological challenges of genome-wide association analysis in Africa","volume":"11","author":"Teo","year":"2010","journal-title":"Nature Reviews Genetics"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08775-0","article-title":"The indirect health effects of malaria estimated from health advantages of the sickle cell trait","volume":"10","author":"Uyoga","year":"2019","journal-title":"Nature Communications"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030158","article-title":"The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya","volume":"3","author":"Wambua","year":"2006","journal-title":"PLOS Medicine"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1056\/NEJM198202113060601","article-title":"Dexamethasone proves deleterious in cerebral malaria","volume":"306","author":"Warrell","year":"1982","journal-title":"New England Journal of Medicine"},{"key":"bib45","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43154","article-title":"Collider bias and the apparent protective effect of glucose-6-phosphate dehydrogenase deficiency on cerebral malaria","volume":"8","author":"Watson","year":"2019","journal-title":"eLife"},{"key":"bib46","article-title":"Kenyan_phenotypic_accuracy","volume-title":"Software Heritage","author":"Watson","year":"2021","unstructured":"Watson JA. 2021. Kenyan_phenotypic_accuracy. Software Heritage. swh:1:rev:03a2de285d38b85a769aa25de46b7960487efc62. https:\/\/archive.softwareheritage.org\/swh:1:dir:236fe424e79fd4d45db768d96e140070d5e1c025;origin=https:\/\/github.com\/jwatowatson\/Kenyan_phenotypic_accuracy;visit=swh:1:snp:c763ec5d56fcbceab1e3f6b1b97b56791289f294;anchor=swh:1:rev:03a2de285d38b85a769aa25de46b7960487efc62."},{"key":"bib47","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1093\/infdis\/jit116","article-title":"Lethal malaria: Marchiafava and Bignami were right","volume":"208","author":"White","year":"2013","journal-title":"Journal of Infectious Diseases"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1038\/ng1660","article-title":"Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait","volume":"37","author":"Williams","year":"2005","journal-title":"Nature Genetics"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.pt.2011.02.004","article-title":"Sickle cell disease and malaria morbidity: a tale with two tails","volume":"27","author":"Williams","year":"2011","journal-title":"Trends in Parasitology"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/tmi.12313_2","article-title":"Severe malaria","volume":"19","author":"World Health Organisation","year":"2014","journal-title":"Tropical Medicine & International Health"},{"key":"bib51","doi-asserted-by":"crossref","DOI":"10.30875\/60123dd4-en","volume-title":"World Malaria Report 2020: 20 Years of Global Progress and Challenges","author":"World Health Organization","year":"2020","unstructured":"World Health Organization. 2020. World Health Organization. World Malaria Report 2020: 20 Years of Global Progress and Challenges."},{"key":"bib52","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1038\/nprot.2007.366","article-title":"Designing candidate gene and genome-wide case-control association studies","volume":"2","author":"Zondervan","year":"2007","journal-title":"Nature Protocols"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/69698\/elife-69698-v3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/69698\/elife-69698-v3.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/69698","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:18:52Z","timestamp":1697059132000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/69698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,6]]},"references-count":52,"alternative-id":["10.7554\/eLife.69698"],"URL":"https:\/\/doi.org\/10.7554\/elife.69698","archive":["CLOCKSS"],"relation":{"references":[{"id-type":"accession","id":"EGAD00010001742","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"doi","id":"10.7910\/DVN\/TH8WAW","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.69698.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.69698.sa2","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.04.16.440107","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,6]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e69698"}}