ArticleNature2015
A novel locus of resistance to severe malaria in a region of ancient balancing selection.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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124 citing papers in PubMed, 223 citations in OpenAlex.
- High-throughput genotyping assays for identification of glycophorin B deletion variants in population studies.Experimental biology and medicine (Maywood, N.J.) · 2021Trial
- Genetic Determinants of Infectious Diseases in the Qatari Population.Epidemiologia (Basel, Switzerland) · 2026Article
- Associations between the Plasmodium falciparum genome and sickle haemoglobin identified in mild malaria cases from Ghana.Malaria journal · 2026Article
- Evolution of Resistance to Avian Malaria Infection in an Endemic Hawaiian Honeycreeper.Ecology and evolution · 2026Article
- Adaptive admixture at ACKR1, the Duffy blood group locus, may have shaped Plasmodium vivax prevalence in Oman.American journal of human genetics · 2026Article
- Article
- Distinct Co-methylation Patterns in African and European Populations and Their Genetic Associations.Genomics, proteomics & bioinformatics · 2025Article
- An ApiAP2 Family Transcriptional Factor PfAP2-06B Regulates Erythrocyte Invasion Indirectly inPathogens (Basel, Switzerland) · 2025Article
- Human genetic variations conferring resistance to malaria.Journal of translational medicine · 2025Review
- Mendelian Randomization and Infection: Pitfalls and Promises.The Journal of infectious diseases · 2025Review
- Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries.BMC genomics · 2025Article
- Unraveling an enhancer-silencer regulatory element showing epistatic interaction with a variant that escaped genome-wide association studies.Cell genomics · 2025Article
- A metabolite-based resistance mechanism against malaria.Science (New York, N.Y.) · 2025Article
- Single-cell transcriptomics reveals inter-ethnic variation in immune response to Falciparum malaria.American journal of human genetics · 2025Article
- Relation Between the Dantu Blood Group Variant and Bacteremia in Kenyan Children: A Population-Based Case-Control Study.The Journal of infectious diseases · 2025Article
- Article
- From Genome-wide Association Studies to Functional Variants: ARL14 Cis-regulatory Variants Are Associated With Severe Malaria.The Journal of infectious diseases · 2024Article
- Lack of Association of TLR1 and TLR5 Coding Variants with Mortality in a Large Multicenter Cohort of Melioidosis Patients.The American journal of tropical medicine and hygiene · 2024Article
- Dantu Blood Group Erythrocytes Form Large Plasmodium falciparum Rosettes Less Commonly.The American journal of tropical medicine and hygiene · 2024Article
- A novel locus inFrontiers in genetics · 2024Article
64 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
Funding
Abstract
The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-threatening Plasmodium falciparum infection (severe malaria) in over 11,000 African children, with replication data in a further 14,000 individuals. Here we report a novel malaria resistance locus close to a cluster of genes encoding glycophorins that are receptors for erythrocyte invasion by P. falciparum. We identify a haplotype at this locus that provides 33% protection against severe malaria (odds ratio = 0.67, 95% confidence interval = 0.60-0.76, P value = 9.5 × 10(-11)) and is linked to polymorphisms that have previously been shown to have features of ancient balancing selection, on the basis of haplotype sharing between humans and chimpanzees. Taken together with previous observations on the malaria-protective role of blood group O, these data reveal that two of the strongest GWAS signals for severe malaria lie in or close to genes encoding the glycosylated surface coat of the erythrocyte cell membrane, both within regions of the genome where it appears that evolution has maintained diversity for millions of years. These findings provide new insights into the host-parasite interactions that are critical in determining the outcome of malaria infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.