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The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Single nucleotide polymorphisms in HLA alleles are associated with HIV-1 viral load in demographically diverse, ART-naïve participants from the START trial

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The impact of variation in host genetics on replication of HIV-1 in demographically diverse populations remains uncertain. Here, we perform a genome-wide screen for associations of single nucleotide polymorphisms (SNP) to viral load (VL) in antiretroviral therapy-naïve participants (n=2,440) with varying demographics from the Strategic Timing of AntiRetroviral Treatment (START) trial. Associations were assessed using genotypic data generated by a customized SNP array, imputed human leukocyte antigen (HLA) alleles and multiple linear regression. Genome-wide significant associations between SNPs and VL were observed in the major histocompatibility complex (MHC) class I region with effect sizes ranging between 0.14-0.39 log10 VL. Supporting the SNP findings, we identified several HLA alleles significantly associated with VL, extending prior observations that the MHC I region is a major host determinant of HIV-1 control with shared genetic variants across diverse populations and underscoring the limitations of GWAS being merely a screening tool.

Original languageEnglish
JournalThe Journal of infectious diseases
Publication statusE-pub ahead of print - 13 Jun 2019

ID: 57419112