ArticlePloS one
Genome-Wide Association Study of HIV Whole Genome Sequences Validated using Drug Resistance.
Article in PloS one. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Novel integrase mutations linked to genotypic DTG resistance in African non-B HIV-1 strains: the DTG RESIST study.The Journal of antimicrobial chemotherapy · 2026Article
- Novel integrase mutations linked to genotypic DTG resistance in non-B HIV-1 strains from African participants: The DTG RESIST study.medRxiv : the preprint server for health sciences · 2025Article
- Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections.PLoS computational biology · 2024Article
- HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre study (DTG RESIST).BMJ open · 2024Article
- Detecting patterns of accessory genome coevolution in Staphylococcus aureus using data from thousands of genomes.BMC bioinformatics · 2023Article
- Human Immunotypes Impose Selection on Viral Genotypes Through Viral Epitope Specificity.The Journal of infectious diseases · 2021Article
- Genetic variation and function: revealing potential factors associated with microbial phenotypes.Biophysics reports · 2021Article
- Epstein-Barr Virus Genomes Reveal Population Structure and Type 1 Association with Endemic Burkitt Lymphoma.Journal of virology · 2020Article
- Benchmarking bacterial genome-wide association study methods using simulated genomes and phenotypes.Microbial genomics · 2020Article
- Review
- Genetic and metabolic signatures of Salmonella enterica subsp. enterica associated with animal sources at the pangenomic scale.BMC genomics · 2019Article
- Current Affairs of Microbial Genome-Wide Association Studies: Approaches, Bottlenecks and Analytical Pitfalls.Frontiers in microbiology · 2019Review
- A phylogenetic method to perform genome-wide association studies in microbes that accounts for population structure and recombination.PLoS computational biology · 2018Article
- Tetraspanins, Another Piece in the HIV-1 Replication Puzzle.Frontiers in immunology · 2018Review
- Clinical and biological insights from viral genome sequencing.Nature reviews. Microbiology · 2017Review
- Microbial genome-wide association studies: lessons from human GWAS.Nature reviews. Genetics · 2017Review
- From Sequence Data to Patient Result: A Solution for HIV Drug Resistance Genotyping With Exatype, End to End Software for Pol-HIV-1 Sanger Based Sequence Analysis and Patient HIV Drug Resistance Result Generation.Journal of the International Association of Providers of AIDS CareArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundGenome-wide association studies (GWAS) have considerably advanced our understanding of human traits and diseases. With the increasing availability of whole genome sequences (WGS) for pathogens, it is important to establish whether GWAS of viral genomes could reveal important biological insights. Here we perform the first proof of concept viral GWAS examining drug resistance (DR), a phenotype with well understood genetics.
methodWe performed a GWAS of DR in a sample of 343 HIV subtype C patients failing 1st line antiretroviral treatment in rural KwaZulu-Natal, South Africa. The majority and minority variants within each sequence were called using PILON, and GWAS was performed within PLINK. HIV WGS from patients failing on different antiretroviral treatments were compared to sequences derived from individuals naïve to the respective treatment.
resultsGWAS methodology was validated by identifying five associations on a genetic level that led to amino acid changes known to cause DR. Further, we highlighted the ability of GWAS to identify epistatic effects, identifying two replicable variants within amino acid 68 of the reverse transcriptase protein previously described as potential fitness compensatory mutations. A possible additional DR variant within amino acid 91 of the matrix region of the Gag protein was associated with tenofovir failure, highlighting GWAS's ability to identify variants outside classical candidate genes. Our results also suggest a polygenic component to DR.
conclusionsThese results validate the applicability of GWAS to HIV WGS data even in relative small samples, and emphasise how high throughput sequencing can provide novel and clinically relevant insights. Further they suggested that for viruses like HIV, population structure was only minor concern compared to that seen in bacteria or parasite GWAS. Given the small genome length and reduced burden for multiple testing, this makes HIV an ideal candidate for GWAS.
Identifiers
What OpenQuestion holds
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.