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

## TL;DR

This study identifies multiple genes and mutations linked to insecticide resistance in West African malaria mosquitoes, showing resistance varies between populations.

## Contribution

The study reveals novel multi-allelic and population-specific genetic loci associated with resistance to two insecticides in Anopheles mosquitoes.

## Key findings

- Resistance to deltamethrin is associated with Cyp6aa1 through copy number variants in An. coluzzii and a non-CNV haplotype in An. gambiae.
- Pirimiphos-methyl resistance involves Ace1, cytochrome P450s, glutathione S-transferases, and nAChR target sites.
- Cyp9k1 and Tep family genes show cross-resistance to both insecticides.

## 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.

Insecticide resistance in mosquitoes threatens the success of malaria control programmes. This study found that in different populations of a malaria mosquito species in West Africa, resistance is associated with different genes or different mutations in the same set of genes.