Open AccessWhole 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 deBruyn,
Nelly Mugo,
James I. Mullins,
M. Juliana McElrath,
Jared M. Baeten,
Connie Celum,
Mary J. Emond,
Jairam R. Lingappa,
Hiv Transmission Study
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