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Review
. 2023 Nov 27;11(12):2866.
doi: 10.3390/microorganisms11122866.

Genome-Wide Association Studies (GWAS) Approaches for the Detection of Genetic Variants Associated with Antibiotic Resistance: A Systematic Review

Jeanneth Mosquera-Rendón  1   2 , Claudia Ximena Moreno-Herrera  2 , Jaime Robledo  1 , Uriel Hurtado-Páez  1
Affiliations
Review

Genome-Wide Association Studies (GWAS) Approaches for the Detection of Genetic Variants Associated with Antibiotic Resistance: A Systematic Review

Jeanneth Mosquera-Rendón et al. Microorganisms. .

Abstract

Antibiotic resistance is a significant threat to public health worldwide. Genome-wide association studies (GWAS) have emerged as a powerful tool to identify genetic variants associated with this antibiotic resistance. By analyzing large datasets of bacterial genomes, GWAS can provide valuable insights into the resistance mechanisms and facilitate the discovery of new drug targets. The present study aimed to undertake a systematic review of different GWAS approaches used for detecting genetic variants associated with antibiotic resistance. We comprehensively searched the PubMed and Scopus databases to identify relevant studies published from 2013 to February 2023. A total of 40 studies met our inclusion criteria. These studies explored a wide range of bacterial species, antibiotics, and study designs. Notably, most of the studies were centered around human pathogens such as Mycobacterium tuberculosis, Escherichia coli, Neisseria gonorrhoeae, and Staphylococcus aureus. The review seeks to explore the several GWAS approaches utilized to investigate the genetic mechanisms associated with antibiotic resistance. Furthermore, it examines the contributions of GWAS approaches in identifying resistance-associated genetic variants through binary and continuous phenotypes. Overall, GWAS holds great potential to enhance our understanding of bacterial resistance and improve strategies to combat infectious diseases.

Keywords: antimicrobial resistance; bacteria; genetic variants; genome-wide association study.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram for the literature review process and selected studies.
Figure 2
Figure 2
Schematic of a Genome-Wide Association Analysis (GWAS) in Bacteria for Identifying Genetic Variants Associated with Antibiotic Resistance. (1) The process starts with the recollection of a diverse collection of bacterial isolates representative of the population under study. (2) Subsequently, the evaluation of resistance to drugs is conducted through established susceptibility tests. Each isolate in the collection undergoes these tests. (3) Concurrently, next-generation sequencing is employed for whole genome sequencing of each isolate in the collection. (4) From the obtained sequences, genetic variants are identified, including SNPs and indels, as well as the presence or absence of genes within each of the isolates. (5) Following this, analyses are performed to ascertain the association between genetic variants and antibiotic resistance traits. This is executed through the GWAS approach, and/or (6) Genetic variants displaying statistically significant associations with drug resistance can be verified using various methodologies: supplementary datasets of bacterial isolates, genetic, molecular, or functional experiments, along with bioinformatic analyses, can be employed to corroborate these associations.
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Grants and funding

This work was supported by Ministerio de Ciencia, Tecnología e Innovación de Colombia (Minciencias) under Project Code 221389666216 CT-783-2018. J.M. received a Ph.D. scholarship from Fondo de Ciencia, Tecnología e Innovación del Sistema General de Regalías (Programa de Excelencia Doctoral del Bicentenario).

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