Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with a range of human diseases and traits. However, understanding the mechanisms by which these genetic variants have an impact on associated diseases and traits, often referred to as the variant-to-function (V2F) problem, remains a significant hurdle. Solving the V2F challenge requires us to identify causative genetic variants, relevant cell types/states, target genes, and mechanisms by which variants can cause diseases or alter phenotypic traits. We discuss emerging functional approaches that are being applied to tackle the V2F problem for blood cell traits, illuminating how human genetic variation can impact on key mechanisms in hematopoiesis, as well as highlighting future prospects for this nascent field.

全基因组关联研究 (GWAS) 已经确定了与一系列人类疾病和特征相关的数千种遗传变异。然而，了解这些遗传变异对相关疾病和性状产生影响的机制，通常被称为变异功能 (V2F) 问题，仍然是一个重大障碍。解决 V2F 挑战需要我们确定致病基因变异、相关细胞类型/状态、靶基因以及变异导致疾病或改变表型特征的机制。我们讨论了正在应用于解决血细胞特征 V2F 问题的新兴功能方法，阐明人类遗传变异如何影响造血的关键机制，并强调这个新兴领域的未来前景。