Diabetes Center, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Genome Med. 2009 Mar 11;1(3):31. doi: 10.1186/gm31.
The extent to which common variants contribute to common phenotypes and disease in humans has important consequences for the future of medical genomics. Two reports have recently clarified this issue for one of the most pressing public health concerns, obesity. These large and comprehensive genome-wide association studies find that common variants within at least 11 genes are associated with obesity. Interestingly, most of these genes are highly expressed in the central nervous system, further highlighting its role in the pathogenesis of obesity. However, the individual and combined effects of these variants explain only a small fraction of the inherited variability in obesity, suggesting that rare variants may contribute significantly to the genetic predisposition for this condition.
常见变异在多大程度上导致人类的常见表型和疾病，这对医学基因组学的未来具有重要意义。最近有两份报告澄清了这个问题，涉及到最紧迫的公共卫生问题之一，即肥胖症。这些大型的、全面的全基因组关联研究发现，至少 11 个基因内的常见变异与肥胖症有关。有趣的是，这些基因中的大多数在中枢神经系统中高度表达，进一步强调了其在肥胖症发病机制中的作用。然而，这些变异的个体和综合效应仅能解释肥胖症遗传变异性的一小部分，这表明罕见变异可能对这种疾病的遗传易感性有重要贡献。
