Department of Preventive Medicine, Keck School of Medicine and the Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
Curr Opin Genet Dev. 2010 Jun;20(3):330-5. doi: 10.1016/j.gde.2010.02.007. Epub 2010 Mar 30.
Incidence rates for many cancers differ markedly by race/ethnicity and furthering our understanding of the genetic and environmental causes of such disparities is a scientific and public health need. Genome-wide association studies (GWAS) are widely acknowledged to provide important information about the etiology of common cancers. To date, these studies have been primarily conducted in European-derived populations. There are important reasons for extending the reach of GWAS studies to other groups and for conducting multiethnic genetic studies involving multiple populations and admixed populations. These include a (1) need to discover the full scope of variants that affect risk of disease in all populations, (2) furthering the understanding of disease pathways, and (3) to assist in fine-mapping of genetic associations by exploiting the differences in linkage disequilibrium between populations to narrow the range of marker alleles demarking regions that contain a true biologically relevant variant. Challenges to multiethnic studies relating to study power, control for hidden population structure, imputation, and use of shared controls for multiple cancer endpoints are discussed.
许多癌症的发病率因种族/民族而异,深入了解造成这种差异的遗传和环境原因是科学和公共卫生的需要。全基因组关联研究(GWAS)被广泛认为提供了有关常见癌症病因的重要信息。迄今为止,这些研究主要在欧洲裔人群中进行。将 GWAS 研究扩展到其他群体并进行涉及多个群体和混合群体的多民族遗传研究有重要的原因。其中包括:(1) 需要发现影响所有人群疾病风险的全部变异范围;(2) 进一步了解疾病途径;(3) 通过利用人群之间连锁不平衡的差异来缩小标记等位基因的范围,从而确定包含真正生物学相关变异的区域,从而协助对遗传关联进行精细映射。讨论了与研究能力、隐藏人口结构控制、推断以及多个癌症终点的共享对照有关的多民族研究的挑战。