Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii

Eric R. Lucas (), Sanjay C. Nagi, Alexander Egyir-Yawson, John Essandoh, Samuel Dadzie, Joseph Chabi, Luc S. Djogbénou, Adandé A. Medjigbodo, Constant V. Edi, Guillaume K. Kétoh, Benjamin G. Koudou, Arjen E. Van’t Hof, Emily J. Rippon, Dimitra Pipini, Nicholas J. Harding, Naomi A. Dyer, Louise T. Cerdeira, Chris S. Clarkson, Dominic P. Kwiatkowski, Alistair Miles, Martin J. Donnelly () and David Weetman ()
Additional contact information
Eric R. Lucas: Liverpool School of Tropical Medicine
Sanjay C. Nagi: Liverpool School of Tropical Medicine
Alexander Egyir-Yawson: University of Cape Coast
John Essandoh: University of Cape Coast
Samuel Dadzie: University of Ghana
Joseph Chabi: University of Ghana
Luc S. Djogbénou: Université d’Abomey-Calavi (UAC)
Adandé A. Medjigbodo: Université d’Abomey-Calavi (UAC)
Constant V. Edi: Centre Suisse de Recherches Scientifiques en Côte d’Ivoire
Guillaume K. Kétoh: Université de Lomé
Benjamin G. Koudou: Centre Suisse de Recherches Scientifiques en Côte d’Ivoire
Arjen E. Van’t Hof: Liverpool School of Tropical Medicine
Emily J. Rippon: Liverpool School of Tropical Medicine
Dimitra Pipini: Liverpool School of Tropical Medicine
Nicholas J. Harding: University of Oxford
Naomi A. Dyer: Liverpool School of Tropical Medicine
Louise T. Cerdeira: Liverpool School of Tropical Medicine
Chris S. Clarkson: Hinxton
Dominic P. Kwiatkowski: Hinxton
Alistair Miles: Hinxton
Martin J. Donnelly: Liverpool School of Tropical Medicine
David Weetman: Liverpool School of Tropical Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gambiae and An. coluzzii from ten locations in West Africa. Resistance was highly multi-genic, multi-allelic and variable between populations. While the strongest and most consistent association with deltamethrin resistance came from Cyp6aa1, this was based on several independent copy number variants (CNVs) in An. coluzzii, and on a non-CNV haplotype in An. gambiae. For pirimiphos-methyl, signals included Ace1, cytochrome P450s, glutathione S-transferases and the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes showed evidence of cross-resistance to both insecticides. These locally-varying, multi-allelic patterns highlight the challenges involved in genomic monitoring of resistance, and may form the basis for improved surveillance methods.

Date: 2023
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DOI: 10.1038/s41467-023-40693-0

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