ArticlePloS one2014
A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Genetic diversity, population structure, and drug resistance of Plasmodium falciparum in Kenya: a systematic review and meta-analysis.Malaria journal · 2025Pooled it
- Genetic diversity of Plasmodium falciparum helical interspersed subtelomeric (phistb) gene in Tanzania and neighboring countries.Malaria journal · 2026Article
- An ApiAP2 Family Transcriptional Factor PfAP2-06B Regulates Erythrocyte Invasion Indirectly inPathogens (Basel, Switzerland) · 2025Article
- Article
- Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.Nature communications · 2024Article
- Unraveling the complexities of ApiAP2 regulation in Plasmodium falciparum.Trends in parasitology · 2024Review
- Article
- MalariaSED: a deep learning framework to decipher the regulatory contributions of noncoding variants in malaria parasites.Genome biology · 2023Article
- Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda.Nature communications · 2022Article
- Integration of population and functional genomics to understand mechanisms of artemisinin resistance in Plasmodium falciparum.International journal for parasitology. Drugs and drug resistance · 2021Article
- The Plasmodium falciparum Rh5 invasion protein complex reveals an excess of rare variant mutations.Malaria journal · 2021Article
- Genomic and Genetic Approaches to Studying Antimalarial Drug Resistance and Plasmodium Biology.Trends in parasitology · 2021Review
- An open dataset ofWellcome open research · 2021Article
- Review
- ApiAP2 Transcription Factors in Apicomplexan Parasites.Pathogens (Basel, Switzerland) · 2019Review
- Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.Science (New York, N.Y.) · 2018Article
- Article
- Overlap Extension Barcoding for the Next Generation Sequencing and Genotyping of Plasmodium falciparum in Individual Patients in Western Kenya.Scientific reports · 2017Article
- Exceptionally long-range haplotypes in Plasmodium falciparum chromosome 6 maintained in an endemic African population.Malaria journal · 2016Article
- Genome-wide association analysis identifies genetic loci associated with resistance to multiple antimalarials in Plasmodium falciparum from China-Myanmar border.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundDrug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA) of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial drugs. METHODS AND PRINCIPAL
findingsParasites isolated from children with acute febrile malaria were adapted to culture, and sensitivity was determined by in vitro growth in the presence of anti-malarial drugs. Parasites were genotyped using whole genome sequencing techniques. Associations between 6250 single nucleotide polymorphisms (SNPs) and resistance to individual anti-malarial agents were determined, with false discovery rate adjustment for multiple hypothesis testing. We identified expected associations in the pfcrt region with chloroquine (CQ) activity, and other novel loci associated with amodiaquine, quinazoline, and quinine activities. Signals for CQ and primaquine (PQ) overlap in and around pfcrt, and interestingly the phenotypes are inversely related for these two drugs. We catalog the variation in dhfr, dhps, mdr1, nhe, and crt, including novel SNPs, and confirm the presence of a dhfr-164L quadruple mutant in coastal Kenya. Mutations implicated in sulfadoxine-pyrimethamine resistance are at or near fixation in this sample set. CONCLUSIONS/SIGNIFICANCE: Sequence-based GWA studies are powerful tools for phenotypic association tests. Using this approach on falciparum parasites from coastal Kenya we identified known and previously unreported genes associated with phenotypic resistance to anti-malarial drugs, and observe in high-resolution haplotype visualizations a possible signature of an inverse selective relationship between CQ and PQ.
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Registered trials
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.