Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.
OBJECTIVE: To date, CCR5 variants remain the only human genetic factors to be confirmed to impact HIV-1 acquisition. However, protective CCR5 variants are largely absent in African populations, in which sporadic resistance to HIV-1 infection is still unexplained. We investigated whether common genet...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1826289727733497856 |
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| author | Petrovski, S Fellay, J Shianna, K Carpenetti, N Kumwenda, J Kamanga, G Kamwendo, D Letvin, N Mcmichael, A Haynes, B Cohen, MS Goldstein, D |
| author_facet | Petrovski, S Fellay, J Shianna, K Carpenetti, N Kumwenda, J Kamanga, G Kamwendo, D Letvin, N Mcmichael, A Haynes, B Cohen, MS Goldstein, D |
| author_sort | Petrovski, S |
| collection | OXFORD |
| description | OBJECTIVE: To date, CCR5 variants remain the only human genetic factors to be confirmed to impact HIV-1 acquisition. However, protective CCR5 variants are largely absent in African populations, in which sporadic resistance to HIV-1 infection is still unexplained. We investigated whether common genetic variants associate with HIV-1 susceptibility in Africans. METHODS: We performed a genome-wide association study (GWAS) in a population of 1532 individuals from Malawi, a country with high prevalence of HIV-1 infection. Using single-nucleotide polymorphisms (SNPs) present on the genome-wide chip, we also investigated previously reported associations with HIV-1 susceptibility or acquisition. Recruitment was coordinated by the Center for HIV/AIDS Vaccine Immunology at two sexually transmitted infection clinics. HIV status was determined by HIV rapid tests and nucleic acid testing. RESULTS: After quality control, the population consisted of 848 high-risk seronegative and 531 HIV-1 seropositive individuals. Logistic regression testing in an additive genetic model was performed for SNPs that passed quality control. No single SNP yielded a significant P value after correction for multiple testing. The study was sufficiently powered to detect markers with genotype relative risk 2.0 or more and minor allele frequencies 12% or more. CONCLUSION: This is the first GWAS of host determinants of HIV-1 susceptibility, performed in an African population. The absence of any significant association can have many possible explanations: rarer genetic variants or common variants with weaker effect could be responsible for the resistance phenotype; alternatively, resistance to HIV-1 infection might be due to nongenetic parameters or to complex interactions between genes, immunity and environment. |
| first_indexed | 2024-03-07T02:33:18Z |
| format | Journal article |
| id | oxford-uuid:a7f63dce-21a5-4ebf-bb5c-1da26f08652e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:33:18Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:a7f63dce-21a5-4ebf-bb5c-1da26f08652e2022-03-27T02:58:06ZCommon human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a7f63dce-21a5-4ebf-bb5c-1da26f08652eEnglishSymplectic Elements at Oxford2011Petrovski, SFellay, JShianna, KCarpenetti, NKumwenda, JKamanga, GKamwendo, DLetvin, NMcmichael, AHaynes, BCohen, MSGoldstein, DOBJECTIVE: To date, CCR5 variants remain the only human genetic factors to be confirmed to impact HIV-1 acquisition. However, protective CCR5 variants are largely absent in African populations, in which sporadic resistance to HIV-1 infection is still unexplained. We investigated whether common genetic variants associate with HIV-1 susceptibility in Africans. METHODS: We performed a genome-wide association study (GWAS) in a population of 1532 individuals from Malawi, a country with high prevalence of HIV-1 infection. Using single-nucleotide polymorphisms (SNPs) present on the genome-wide chip, we also investigated previously reported associations with HIV-1 susceptibility or acquisition. Recruitment was coordinated by the Center for HIV/AIDS Vaccine Immunology at two sexually transmitted infection clinics. HIV status was determined by HIV rapid tests and nucleic acid testing. RESULTS: After quality control, the population consisted of 848 high-risk seronegative and 531 HIV-1 seropositive individuals. Logistic regression testing in an additive genetic model was performed for SNPs that passed quality control. No single SNP yielded a significant P value after correction for multiple testing. The study was sufficiently powered to detect markers with genotype relative risk 2.0 or more and minor allele frequencies 12% or more. CONCLUSION: This is the first GWAS of host determinants of HIV-1 susceptibility, performed in an African population. The absence of any significant association can have many possible explanations: rarer genetic variants or common variants with weaker effect could be responsible for the resistance phenotype; alternatively, resistance to HIV-1 infection might be due to nongenetic parameters or to complex interactions between genes, immunity and environment. |
| spellingShingle | Petrovski, S Fellay, J Shianna, K Carpenetti, N Kumwenda, J Kamanga, G Kamwendo, D Letvin, N Mcmichael, A Haynes, B Cohen, MS Goldstein, D Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. |
| title | Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. |
| title_full | Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. |
| title_fullStr | Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. |
| title_full_unstemmed | Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. |
| title_short | Common human genetic variants and HIV-1 susceptibility: a genome-wide survey in a homogeneous African population. |
| title_sort | common human genetic variants and hiv 1 susceptibility a genome wide survey in a homogeneous african population |
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