Manolio Teri A, Collins Francis S
National Human Genome Research Institute, Bethesda, Maryland 20892, USA,
Annu Rev Med. 2009;60:443-56. doi: 10.1146/annurev.med.60.061907.093117.
The International HapMap Project produced a genome-wide database of human genetic variation for use in genetic association studies of common diseases. The initial output of these studies has been overwhelming, with over 150 risk loci identified in studies of more than 60 common diseases and traits. These associations have suggested previously unsuspected etiologic pathways for common diseases that will be of use in identifying new therapeutic targets and developing targeted interventions based on genetically defined risk. Here we examine the development and application of the HapMap to genome-wide association (GWA) studies; present and future technologies for GWA research; current major efforts in GWA studies; successes and limitations of the GWA approach in identifying polymorphisms related to complex diseases; data release and privacy polices; use of these findings by clinicians, the public, and academic physicians; and sources of ongoing authoritative information on this rapidly evolving field.
国际人类基因组单体型图计划生成了一个全基因组人类遗传变异数据库，用于常见疾病的基因关联研究。这些研究的初步成果极为丰硕，在对60多种常见疾病和性状的研究中已确定了150多个风险位点。这些关联提示了常见疾病此前未被怀疑的病因途径，这将有助于识别新的治疗靶点，并基于基因定义的风险开发针对性干预措施。在此，我们探讨了人类基因组单体型图在全基因组关联（GWA）研究中的发展与应用；GWA研究的现有及未来技术；GWA研究当前的主要工作；GWA方法在识别与复杂疾病相关的多态性方面的成功与局限；数据发布和隐私政策；临床医生、公众及学术医生对这些研究结果的使用；以及关于这个快速发展领域的现行权威信息来源。
