GWATCH: a web platform for automated gene association discovery analysis

Svitin, Anton; Malov, Sergey V.; Cherkasov, Nikolay; Geerts, Paul; Rotkevich, Mikhail; Dobrynin, Pavel; Shevchenko, Andrey; Guan, Li; Troyer, Jennifer L.; Hendrickson, Sher L.; Dilks, Holli H.; Oleksyk, Tarás K.; Donfield, Sharyne; Gomperts, Edward D.; Jabs, Douglas A.; Sezgın, Efe; Natta, Mark Van; Harrigan, P. Richard; Brumme, Zabrina L.; O’Brien, Stephen J.

doi:10.1186/2047-217x-3-18

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…3), we used GWATCH, a software platform designed to automate, display, and replicate GWAS analyses within chromosomal regions. 22 We also examined the SNPs around CCNG1 and HCG22 using GWAS results from American HIV/AIDS cohorts ( Supplementary Fig. S10).…”

Section: Resultsmentioning

confidence: 99%

“…For the replication study on HIV susceptibility, two replication cohorts, including 4,462 European Americans and 1,460 African Americans subjected to published GWASs, 8,14,22 were examined using GWATCH in the HCG22 (chr6) and CCNG1 (chr5) gene regions. We also included 809 new Botswana subjects (59 males, 750 females) in the replication study.…”

Section: Cohort and Patient Eligibilitymentioning

confidence: 99%

“…The GWATCH analysis was performed as described. 22 Twenty-four tests were applied to test the association between genotypes and phenotypes ( Supplementary Table S11).…”

Section: Gwatch Analysismentioning

confidence: 99%

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Genome-Wide Analyses Reveal Gene Influence on HIV Disease Progression and HIV-1C Acquisition in Southern Africa

Xie

Agniel

Shevchenko

et al. 2017

AIDS Research and Human Retroviruses

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Sub-Saharan Africans infected with HIV-1C make up the largest AIDS patient population in the world and exhibit large heterogeneity in disease progression before initiating antiretroviral therapy. To identify host variants associated with HIV disease progression, we performed genome-wide association studies on a total of 556 treatment-naive HIV-infected individuals in Botswana. We characterized the pattern of HIV disease progression using a novel functional principal component analysis, which can better capture longitudinal CD4 and viral load (VL) trajectories. Two single-nucleotide polymorphisms (SNPs) near HCG22 (chr6, peak variant rs2535307, combined p = 3.72 × 10, minor allele as risky allele) and CCNG1 (chr5, peak variant kgp22385164, combined p = 1.88 × 10, minor allele as risky allele) were significantly associated with CD4 and VL dynamics. Inspection of SNPs in these gene regions in a third Botswana cohort (using GWATCH) also revealed a strong association of HCG22 with HIV-1C acquisition, suggesting that this region is associated with infection as well as disease progression. Our study uncovered two genetic regions that are significant and have specific effects on HIV-1C acquisition or progression in sub-Saharan Africans, and the result suggested new potential targets for AIDS prevention and treatment. In addition, our results also indicate the possibility of using genetic markers as HIV disease progression indicators in sub-Saharan Africans to prioritize fast progressors for antiretroviral treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Cohort and Patient Eligibilitymentioning

confidence: 99%

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Genome-Wide Analyses Reveal Gene Influence on HIV Disease Progression and HIV-1C Acquisition in Southern Africa

Xie

Agniel

Shevchenko

et al. 2017

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

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Genome-wide association study reveals genetic variants associated with HIV-1C infection in a Botswana study population

Shevchenko

Zhernakova

Malov

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Although there have been many studies of gene variant association with different stages of HIV/AIDS progression in United States and European cohorts, few gene-association studies have assessed genic determinants in sub-Saharan African populations, which have the highest density of HIV infections worldwide. We carried out genome-wide association studies on 766 study participants at risk for HIV-1 subtype C (HIV-1C) infection in Botswana. Three gene associations (AP3B1, PTPRA, and NEO1) were shown to have significant association with HIV-1C acquisition. Each gene association was replicated within Botswana or in the United States–African American or United States–European American AIDS cohorts or in both. Each associated gene has a prior reported influence on HIV/AIDS pathogenesis. Thirteen previously discovered AIDS restriction genes were further replicated in the Botswana cohorts, extending our confidence in these prior AIDS restriction gene reports. This work presents an early step toward the identification of genetic variants associated with and affecting HIV acquisition or AIDS progression in the understudied HIV-1C afflicted Botswana population.

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Legacy of a magic gene— CCR5- ∆ 32 : From discovery to clinical benefit in a generation

OBrien

2024

Proc. Natl. Acad. Sci. U.S.A.

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The discovery of the 32-bp deletion allele of the chemokine receptor gene CCR5 showed that homozygous carriers display near-complete resistance to HIV infection, irrespective of exposure. Algorithms of molecular evolutionary theory suggested that the CCR5- ∆ 32 mutation occurred but once in the last millennium and rose by strong selective pressure relatively recently to a ~10% allele frequency in Europeans. Several lines of evidence support the hypothesis that CCR5- ∆ 32 was selected due to its protective influence to resist Yersinia pestis, the agent of the Black Death/bubonic plague of the 14th century. Powerful anti-AIDS entry inhibitors targeting CCR5 were developed as a treatment for HIV patients, particularly those whose systems had developed resistance to powerful anti-retroviral therapies. Homozygous CCR5- ∆ 32/ ∆ 32 stem cell transplant donors were used to produce HIV-cleared AIDS patients in at least five “cures” of HIV infection. CCR5 has also been implicated in regulating infection with Staphylococcus aureus , in recovery from stroke, and in ablation of the fatal graft versus host disease (GVHD) in cancer transplant patients. While homozygous CCR5- ∆ 32/32 carriers block HIV infection, alternatively they display an increased risk for encephalomyelitis and death when infected with the West Nile virus.

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GWATCH: a web platform for automated gene association discovery analysis

Cited by 5 publications

References 36 publications

Genome-Wide Analyses Reveal Gene Influence on HIV Disease Progression and HIV-1C Acquisition in Southern Africa

Genome-Wide Analyses Reveal Gene Influence on HIV Disease Progression and HIV-1C Acquisition in Southern Africa

Genome-wide association study reveals genetic variants associated with HIV-1C infection in a Botswana study population

Legacy of a magic gene— CCR5- ∆ 32 : From discovery to clinical benefit in a generation

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