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<p>Human Immunodeficiency Virus Type 1 (HIV) set-point viral load is a strong predictor of disease progression and transmission risk. A recent genome-wide association study in individuals of African ancestries identified a region on chromosome 1 significantly associated with decreased HIV set-point viral load. Knockout of the closest gene, <i>CHD1L</i>, enhanced HIV replication in vitro in myeloid cells. However, it remains unclear if HIV spVL associated variants are associated with <i>CHD1L</i> gene expression changes. Here we apply a heuristic fine-mapping approach to prioritize combinations of variants that explain the majority of set-point viral load variance and identify variants likely driving the association. We assess the combined impact of these variants on <i>CHD1L</i> regulation using publicly available sequencing studies, and test the relationship between <i>CHD1L</i> expression and set-point viral load using imputed <i>CHD1L</i> expression from monocytes. Taken together, this work characterizes genetically regulated <i>CHD1L</i> expression and further expands our knowledge of <i>CHD1L</i>-mediated HIV restriction in monocytes.</p>

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Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月17日

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  • Riley H. Tough,
  • Paul J. McLaren

摘要

Human Immunodeficiency Virus Type 1 (HIV) set-point viral load is a strong predictor of disease progression and transmission risk. A recent genome-wide association study in individuals of African ancestries identified a region on chromosome 1 significantly associated with decreased HIV set-point viral load. Knockout of the closest gene, CHD1L, enhanced HIV replication in vitro in myeloid cells. However, it remains unclear if HIV spVL associated variants are associated with CHD1L gene expression changes. Here we apply a heuristic fine-mapping approach to prioritize combinations of variants that explain the majority of set-point viral load variance and identify variants likely driving the association. We assess the combined impact of these variants on CHD1L regulation using publicly available sequencing studies, and test the relationship between CHD1L expression and set-point viral load using imputed CHD1L expression from monocytes. Taken together, this work characterizes genetically regulated CHD1L expression and further expands our knowledge of CHD1L-mediated HIV restriction in monocytes.