{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:37:34Z","timestamp":1777426654923,"version":"3.51.4"},"reference-count":67,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["203077"],"award-info":[{"award-number":["203077"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["084538"],"award-info":[{"award-number":["084538"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["101910\/Z\/13\/Z"],"award-info":[{"award-number":["101910\/Z\/13\/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":["G19\/9"],"award-info":[{"award-number":["G19\/9"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["091758"],"award-info":[{"award-number":["091758"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["202800"],"award-info":[{"award-number":["202800"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["084226"],"award-info":[{"award-number":["084226"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["067431"],"award-info":[{"award-number":["067431"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Malaria has been a major driving force in the evolution of the human genome. In sub-Saharan African populations, two neighbouring polymorphisms in the Complement Receptor One (CR1) gene, named Sl2 and McCb, occur at high frequencies, consistent with selection by malaria. Previous studies have been inconclusive. Using a large case-control study of severe malaria in Kenyan children and statistical models adjusted for confounders, we estimate the relationship between Sl2 and McCb and malaria phenotypes, and find they have opposing associations. The Sl2 polymorphism is associated with markedly reduced odds of cerebral malaria and death, while the McCb polymorphism is associated with increased odds of cerebral malaria. We also identify an apparent interaction between Sl2 and \u03b1+thalassaemia, with the protective association of Sl2 greatest in children with normal \u03b1-globin. The complex relationship between these three mutations may explain previous conflicting findings, highlighting the importance of considering genetic interactions in disease-association studies.<\/jats:p>","DOI":"10.7554\/elife.31579","type":"journal-article","created":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T20:00:11Z","timestamp":1524600011000},"source":"Crossref","is-referenced-by-count":29,"title":["Two complement receptor one alleles have opposing associations with cerebral malaria and interact with \u03b1+thalassaemia"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-4365","authenticated-orcid":true,"given":"D Herbert","family":"Opi","sequence":"first","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"},{"name":"Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-2849","authenticated-orcid":true,"given":"Olivia","family":"Swann","sequence":"additional","affiliation":[{"name":"Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Macharia","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Uyoga","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Band","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyne M","family":"Ndila","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewen M","family":"Harrison","sequence":"additional","affiliation":[{"name":"Centre for Medical Infomatics, Usher Insitute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2679-035X","authenticated-orcid":true,"given":"Mahamadou A","family":"Thera","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Centre, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako, Bamako, Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdoulaye K","family":"Kone","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Centre, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako, Bamako, Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dapa A","family":"Diallo","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Centre, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako, Bamako, Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ogobara K","family":"Doumbo","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Centre, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako, Bamako, Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten E","family":"Lyke","sequence":"additional","affiliation":[{"name":"Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher V","family":"Plowe","sequence":"additional","affiliation":[{"name":"Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joann M","family":"Moulds","sequence":"additional","affiliation":[{"name":"Lifeshare Blood Centers, Shreveport, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Shebbe","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neema","family":"Mturi","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Peshu","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Maitland","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"},{"name":"Department of Medicine, Imperial College, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Raza","sequence":"additional","affiliation":[{"name":"Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic P","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom"},{"name":"Wellcome Trust Sanger Institute, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-9299","authenticated-orcid":true,"given":"Kirk A","family":"Rockett","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4456-2382","authenticated-orcid":true,"given":"Thomas N","family":"Williams","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"},{"name":"Department of Medicine, Imperial College, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-1892","authenticated-orcid":true,"given":"J Alexandra","family":"Rowe","sequence":"additional","affiliation":[{"name":"Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4374","published-online":{"date-parts":[[2018,4,25]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1182\/blood-2013-10-533489","article-title":"Epistasis between the haptoglobin common variant and \u03b1+thalassemia influences risk of severe malaria in Kenyan children","volume":"123","author":"Atkinson","year":"2014","journal-title":"Blood"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"e1003509","DOI":"10.1371\/journal.pgen.1003509","article-title":"Imputation-based meta-analysis of severe malaria in three African populations","volume":"9","author":"Band","year":"2013","journal-title":"PLoS Genetics"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"Journal of Statistical Software"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"e15266","DOI":"10.7554\/eLife.15266","article-title":"Admixture into and within sub-Saharan Africa","volume":"5","author":"Busby","year":"2016","journal-title":"eLife"},{"key":"bib5","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1182\/blood.V84.11.3909.bloodjournal84113909","article-title":"Natural protection against severe Plasmodium falciparum malaria due to impaired rosette formation","volume":"84","author":"Carlson","year":"1994","journal-title":"Blood"},{"key":"bib6","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1182\/blood.V95.1.360","article-title":"Single-tube multiplex-PCR screen for common deletional determinants of alpha-thalassemia","volume":"95","author":"Chong","year":"2000","journal-title":"Blood"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"e15085","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":"Clarke","year":"2017","journal-title":"eLife"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1073\/pnas.0305306101","article-title":"A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria","volume":"101","author":"Cockburn","year":"2004","journal-title":"PNAS"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/j.1537-2995.2007.01077.x","article-title":"Knops blood group haplotypes among distinct Brazilian populations","volume":"47","author":"Covas","year":"2007","journal-title":"Transfusion"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"987","DOI":"10.4269\/ajtmh.2009.09-0406","article-title":"High levels of Plasmodium falciparum rosetting in all clinical forms of severe malaria in African children","volume":"81","author":"Doumbo","year":"2009","journal-title":"American Journal of Tropical Medicine and Hygiene"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/1475-2875-9-119","article-title":"Candidate malaria susceptibility\/protective SNPs in hospital and population-based studies: the effect of sub-structuring","volume":"9","author":"Eid","year":"2010","journal-title":"Malaria Journal"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1038\/nature03631","article-title":"Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria","volume":"435","author":"Fairhurst","year":"2005","journal-title":"Nature"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1177\/1745691612462587","article-title":"The Long Way From \u03b1-Error Control to Validity Proper: Problems With a Short-Sighted False-Positive Debate","volume":"7","author":"Fiedler","year":"2012","journal-title":"Perspectives on Psychological Science : A Journal of the Association for Psychological Science"},{"key":"bib14","doi-asserted-by":"crossref","first-page":"330","DOI":"10.4269\/ajtmh.2004.71.330","article-title":"Large-scale candidate gene study of leprosy susceptibility in the Karonga district of northern Malawi","volume":"71","author":"Fitness","year":"2004","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1371\/journal.pmed.0050056","article-title":"Increased microerythrocyte count in homozygous alpha(+)-thalassaemia contributes to protection against severe malarial anaemia","volume":"5","author":"Fowkes","year":"2008","journal-title":"PLoS Medicine"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1093\/hmg\/ddm331","article-title":"Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria","volume":"17","author":"Fry","year":"2008","journal-title":"Human Molecular Genetics"},{"key":"bib17","first-page":"288","article-title":"Role of CR1 Knops polymorphism in the pathophysiology of malaria: Indian scenario","volume":"46","author":"Gandhi","year":"2009","journal-title":"Journal of Vector Borne Diseases"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1084\/jem.192.12.1797","article-title":"Complement receptor 1\/CD35 is a receptor for mannan-binding lectin","volume":"192","author":"Ghiran","year":"2000","journal-title":"The Journal of Experimental Medicine"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1159\/000108939","article-title":"Graphical tests for Hardy-Weinberg equilibrium based on the ternary plot","volume":"65","author":"Graffelman","year":"2008","journal-title":"Human Heredity"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1186\/1475-2875-12-400","article-title":"Human genetic polymorphisms in the Knops blood group are not associated with a protective advantage against Plasmodium falciparum malaria in Southern Ghana","volume":"12","author":"Hansson","year":"2013","journal-title":"Malaria Journal"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/ng.388","article-title":"Genome-wide and fine-resolution association analysis of malaria in West Africa","volume":"41","author":"Jallow","year":"2009","journal-title":"Nature Genetics"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1111\/epi.12173","article-title":"The genetic risk of acute seizures in African children with falciparum malaria","volume":"54","author":"Kariuki","year":"2013","journal-title":"Epilepsia"},{"key":"bib23","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1182\/blood.V78.3.812.812","article-title":"Rosetting of Plasmodium falciparum-infected red blood cells with uninfected red blood cells enhances microvascular obstruction under flow conditions","volume":"78","author":"Kaul","year":"1991","journal-title":"Blood"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"e37214","DOI":"10.1371\/journal.pone.0037214","article-title":"\u03b1-Thalassemia impairs the cytoadherence of Plasmodium falciparum-infected erythrocytes","volume":"7","author":"Krause","year":"2012","journal-title":"PLoS ONE"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1034\/j.1600-065X.2001.1800110.x","article-title":"Structure-function relationships of complement receptor type 1","volume":"180","author":"Krych-Goldberg","year":"2001","journal-title":"Immunological Reviews"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/S1471-4914(02)02419-X","article-title":"Human complement receptor type 1 (CR1) binds to a major malarial adhesin","volume":"8","author":"Krych-Goldberg","year":"2002","journal-title":"Trends in Molecular Medicine"},{"key":"bib27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.4269\/ajtmh.2003.69.253","article-title":"Association of intraleukocytic Plasmodium falciparum malaria pigment with disease severity, clinical manifestations, and prognosis in severe malaria","volume":"69","author":"Lyke","year":"2003","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nature15390","article-title":"A novel locus of resistance to severe malaria in a region of ancient balancing selection","volume":"526","author":"Malaria Genomic Epidemiology Network","year":"2015","journal-title":"Nature"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"e47463","DOI":"10.1371\/journal.pone.0047463","article-title":"Candidate human genetic polymorphisms and severe malaria in a Tanzanian population","volume":"7","author":"Manjurano","year":"2012","journal-title":"PLoS ONE"},{"key":"bib30","doi-asserted-by":"crossref","first-page":"734","DOI":"10.4269\/ajtmh.2003.68.734","article-title":"Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast","volume":"68","author":"Mbogo","year":"2003","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1111\/j.1537-2995.2004.00615.x","article-title":"Identification of the Kna\/Knb polymorphism and a method for Knops genotyping","volume":"44","author":"Moulds","year":"2004","journal-title":"Transfusion"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"2879","DOI":"10.1182\/blood.V97.9.2879","article-title":"Molecular identification of Knops blood group polymorphisms found in long homologous region D of complement receptor 1","volume":"97","author":"Moulds","year":"2001","journal-title":"Blood"},{"key":"bib33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.21307\/immunohematology-2019-193","article-title":"The Knops blood-group system: a review","volume":"26","author":"Moulds","year":"2010","journal-title":"Immunohematology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1093\/beheco\/arh107","article-title":"A farewell to Bonferroni: the problems of low statistical power and publication bias","volume":"15","author":"Nakagawa","year":"2004","journal-title":"Behavioral Ecology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1111\/j.1537-2995.2011.03161.x","article-title":"Knops blood group polymorphism and susceptibility to Mycobacterium tuberculosis infection","volume":"51","author":"Noumsi","year":"2011","journal-title":"Transfusion"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1093\/ajcn\/80.6.1604","article-title":"Malaria and nutritional status in children living on the coast of Kenya","volume":"80","author":"Nyakeriga","year":"2004","journal-title":"The American Journal of Clinical Nutrition"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1016\/S0140-6736(08)61655-4","article-title":"Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya","volume":"372","author":"O'Meara","year":"2008","journal-title":"The Lancet"},{"key":"bib38","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 alphathalassemia","volume":"1","author":"Opi","year":"2014","journal-title":"EBioMedicine"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/gene.2016.2","article-title":"Red blood cell complement receptor one level varies with Knops blood group, \u03b1(+)thalassaemia and age among Kenyan children","volume":"17","author":"Opi","year":"2016","journal-title":"Genes & Immunity"},{"key":"bib40","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.4049\/jimmunol.141.11.3889","article-title":"Direct evidence for the clustered nature of complement receptors type 1 on the erythrocyte membrane","volume":"141","author":"Paccaud","year":"1988","journal-title":"Journal of Immunology"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"21242","DOI":"10.1073\/pnas.0910840106","article-title":"Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean","volume":"106","author":"Penman","year":"2009","journal-title":"PNAS"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1136\/bmj.316.7139.1236","article-title":"What's wrong with Bonferroni adjustments","volume":"316","author":"Perneger","year":"1998","journal-title":"BMJ"},{"key":"bib43","article-title":"R: A language and environment for statistical computing","author":"R Development Core Team","year":"2010","unstructured":"R Development Core Team. 2010. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. 2.11.1."},{"key":"bib44","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":"Rockett","year":"2014","journal-title":"Nature Genetics"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1097\/00001648-199001000-00010","article-title":"No adjustments are needed for multiple comparisons","volume":"1","author":"Rothman","year":"1990","journal-title":"Epidemiology"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1007\/s11606-013-2755-z","article-title":"Six persistent research misconceptions","volume":"29","author":"Rothman","year":"2014","journal-title":"Journal of General Internal Medicine"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1017\/S1462399409001082","article-title":"Adhesion of Plasmodium falciparum-infected erythrocytes to human cells: molecular mechanisms and therapeutic implications","volume":"11","author":"Rowe","year":"2009","journal-title":"Expert Reviews in Molecular Medicine"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"17471","DOI":"10.1073\/pnas.0705390104","article-title":"Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting","volume":"104","author":"Rowe","year":"2007","journal-title":"PNAS"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/40888","article-title":"P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1","volume":"388","author":"Rowe","year":"1997","journal-title":"Nature"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"6341","DOI":"10.4049\/jimmunol.165.11.6341","article-title":"Mapping of the region of complement receptor (CR) 1 required for Plasmodium falciparum rosetting and demonstration of the importance of CR1 in rosetting in field isolates","volume":"165","author":"Rowe","year":"2000","journal-title":"The Journal of Immunology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.molimm.2015.03.006","article-title":"More than just immune evasion: Hijacking complement by Plasmodium falciparum","volume":"67","author":"Schmidt","year":"2015","journal-title":"Molecular Immunology"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1093\/ije\/dys062","article-title":"Profile: The kilifi health and demographic surveillance system (KHDSS)","volume":"41","author":"Scott","year":"2012","journal-title":"International Journal of Epidemiology"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"e1000968","DOI":"10.1371\/journal.ppat.1000968","article-title":"Complement receptor 1 is a sialic acid-independent erythrocyte receptor of Plasmodium falciparum","volume":"6","author":"Spadafora","year":"2010","journal-title":"PLoS Pathogens"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"17825","DOI":"10.1038\/s41598-017-17664-9","article-title":"No evidence that knops blood group polymorphisms affect complement receptor 1 clustering on erythrocytes","volume":"7","author":"Swann","year":"2017","journal-title":"Scientific Reports"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"e34820","DOI":"10.1371\/journal.pone.0034820","article-title":"Lack of evidence from studies of soluble protein fragments that Knops blood group polymorphisms in complement receptor-type 1 are driven by malaria","volume":"7","author":"Tetteh-Quarcoo","year":"2012","journal-title":"PLoS ONE"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1179\/2047773215Y.0000000011","article-title":"Severity of malaria in relation to a complement receptor 1 polymorphism: a case-control study","volume":"109","author":"Tettey","year":"2015","journal-title":"Pathogens and Global Health"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"17327","DOI":"10.1073\/pnas.1008151107","article-title":"Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand","volume":"107","author":"Tham","year":"2010","journal-title":"PNAS"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/1475-2875-4-54","article-title":"Complement receptor 1 polymorphisms associated with resistance to severe malaria in Kenya","volume":"4","author":"Thathy","year":"2005","journal-title":"Malaria Journal"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"e43987","DOI":"10.1371\/journal.pone.0043987","article-title":"Candidate polymorphisms and severe malaria in a Malian population","volume":"7","author":"Toure","year":"2012","journal-title":"PLoS ONE"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"e119","DOI":"10.1093\/nar\/29.23.e119","article-title":"Single tube genotyping of sickle cell anaemia using PCR-based SNP analysis","volume":"29","author":"Waterfall","year":"2001","journal-title":"Nucleic Acids Research"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-98141-3","volume-title":"Ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2009"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1086\/430744","article-title":"Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases","volume":"192","author":"Williams","year":"2005","journal-title":"The Journal of Infectious Diseases"},{"key":"bib63","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":"bib64","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1016\/S0140-6736(09)61374-X","article-title":"Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case-control study","volume":"374","author":"Williams","year":"2009","journal-title":"The Lancet"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1182\/blood-2005-01-0313","article-title":"Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya","volume":"106","author":"Williams","year":"2005","journal-title":"Blood"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.humimm.2012.10.024","article-title":"The polymorphism of Knops blood group system in Korean population and their relationship with HLA system","volume":"74","author":"Yoon","year":"2013","journal-title":"Human Immunology"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/sj.gene.6363980","article-title":"CR1 Knops blood group alleles are not associated with severe malaria in the Gambia","volume":"4","author":"Zimmerman","year":"2003","journal-title":"Genes & Immunity"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/31579\/elife-31579-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/31579\/elife-31579-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/31579","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:48:46Z","timestamp":1697057326000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/31579"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,25]]},"references-count":67,"alternative-id":["10.7554\/eLife.31579"],"URL":"https:\/\/doi.org\/10.7554\/elife.31579","archive":["CLOCKSS"],"relation":{"references":[{"id-type":"uri","id":"https:\/\/www.malariagen.net\/projects\/consortial-project-1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.31579.025","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.31579.024","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,25]]},"article-number":"e31579"}}