Self-reported neurocognitive complaints in the Swiss HIV Cohort Study – a viral genome wide association study. Brain Communications
People with HIV (PWH) may experience neurocognitive complaints which can significantly impact their quality of life. While these complaints are often multifactorial, the role of the HIV genome in their development has remained unclear. In a study published in Brain Communications, Zeeb et al. conducted the first viral genome-wide association study to explore the genetic basis of self-reported neurocognitive complaints in PWH.
The study analyzed data from 8’547 participants in the Swiss HIV Cohort Study who reported neurocognitive problems such as memory loss, concentration difficulties, or cognitive slowing between 2014 and 2020. Using partial pol sequences and near full-length HIV genomes, the researchers estimated the heritability and identified specific viral genetic variants associated with these complaints.
Overall, 56% of participants reported at least one neurocognitive complaint during the study period, with memory loss being the most common one. The study found that self-reported neurocognitive symptoms are partially heritable through the HIV genome, with heritability estimates ranging from 1% to 22%, depending on the phylogenetic distance threshold and HIV subtype. In addition, a mutation in the HIV envelope protein (Env L641E) was significantly associated with increased memory loss complaints. While only one variant reached statistical significance, several other mutations showed nominal associations with SRNCs, highlighting the complex, polygenic nature of these complaints.
In summary, this research advances our understanding of the pathogenesis of neurocognitive disorders in people with HIV. It provides strong evidence for viral genetic contributions to the variability in neurocognitive complaints, offering new insights into the complex interplay between viral genetics and cognitive health in PWH.