Montreal Heart Institute, Faculté de Médecine, Université de Montréal, 5000 Bélanger Street, Montréal, QC H1T 1C8, Canada.
Genes (Basel). 2014 Jan 27;5(1):51-64. doi: 10.3390/genes5010051.
Genome-wide association studies (GWAS) have identified reproducible genetic associations with hundreds of human diseases and traits. The vast majority of these associated single nucleotide polymorphisms (SNPs) are non-coding, highlighting the challenge in moving from genetic findings to mechanistic and functional insights. Nevertheless, large-scale (epi)genomic studies and bioinformatic analyses strongly suggest that GWAS hits are not randomly distributed in the genome but rather pinpoint specific biological pathways important for disease development or phenotypic variation. In this review, we focus on GWAS discoveries for the three main blood cell types: red blood cells, white blood cells and platelets. We summarize the knowledge gained from GWAS of these phenotypes and discuss their possible clinical implications for common (e.g., anemia) and rare (e.g., myeloproliferative neoplasms) human blood-related diseases. Finally, we argue that blood phenotypes are ideal to study the genetics of complex human traits because they are fully amenable to experimental testing.
全基因组关联研究（GWAS）已经确定了数百种人类疾病和特征与可重复的遗传关联。这些相关的单核苷酸多态性（SNPs）绝大多数是非编码的，这凸显了从遗传发现到机制和功能见解的挑战。然而，大规模（表观）基因组学研究和生物信息学分析强烈表明，GWAS 命中并非随机分布在基因组中，而是精确指出了对疾病发展或表型变异很重要的特定生物学途径。在这篇综述中，我们专注于三种主要血细胞类型（红细胞、白细胞和血小板）的 GWAS 发现。我们总结了这些表型的 GWAS 研究获得的知识，并讨论了它们对常见（例如贫血）和罕见（例如骨髓增生性肿瘤）人类血液相关疾病的可能临床意义。最后，我们认为血液表型是研究复杂人类特征遗传的理想模型，因为它们完全可以进行实验测试。
