Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1 | Zendy

Romel D. Mackelprang | Zendy; Michael J. Bamshad | Zendy; Jessica X. Chong | Zendy; Xuanlin Hou | Zendy; Kati J. Buckingham | Zendy; Kathryn M. Shively | Zendy; Guy de Bruyn | Zendy; Nelly Mugo | Zendy; James I. Mullins | Zendy; M. Juliana McElrath | Zendy; Jared M. Baeten | Zendy; Connie Celum | Zendy; Mary J. Emond | Zendy; Jairam R. Lingappa | Zendy

Open Access

Whole genome sequencing of extreme phenotypes identifies variants in CD101 and UBE2V1 associated with increased risk of sexually acquired HIV-1

Author(s) -

Romel D. Mackelprang,

Michael J. Bamshad,

Jessica X. Chong,

Xuanlin Hou,

Kati J. Buckingham,

Kathryn M. Shively,

Guy de Bruyn,

Nelly Mugo,

James I. Mullins,

M. Juliana McElrath,

Jared M. Baeten,

Connie Celum,

Mary J. Emond,

Jairam R. Lingappa

Publication year - 2017

Publication title -

plos pathogens

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.719

H-Index - 206

eISSN - 1553-7374

pISSN - 1553-7366

DOI - 10.1371/journal.ppat.1006703

Subject(s) - missense mutation , biology , genome wide association study , phenotype , gene , genetics , human immunodeficiency virus (hiv) , dna sequencing , genotyping , single nucleotide polymorphism , genome , genotype , virology

Host genetic variation modifying HIV-1 acquisition risk can inform development of HIV-1 prevention strategies. However, associations between rare or intermediate-frequency variants and HIV-1 acquisition are not well studied. We tested for the association between variation in genic regions and extreme HIV-1 acquisition phenotypes in 100 sub-Saharan Africans with whole genome sequencing data. Missense variants in immunoglobulin-like regions of CD101 and, among women, one missense/5’ UTR variant in UBE2V1 , were associated with increased HIV-1 acquisition risk (p = 1.9x10 -4 and p = 3.7x10 -3 , respectively, for replication). Both of these genes are known to impact host inflammatory pathways. Effect sizes increased with exposure to HIV-1 after adjusting for the independent effect of increasing exposure on acquisition risk. Trial registration : ClinicalTrials.gov NCT00194519 ; NCT00557245

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