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

Eric Lucas, Sanjay 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 Rippon, Dimitra Pipini, Nicholas J. Harding, Naomi Dyer, Louise Cerdeira, Chris S. Clarkson, Dominic P. Kwiatkowski, Alistair MilesMartin Donnelly, David Weetman

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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, multiallelic 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 form the basis for improved surveillance methods.

Original languageEnglish
Article number4946
Pages (from-to)e4946
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 16 Aug 2023

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