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

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 = 1.9x10-4and 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. © 2017 mackelprang et al.