Division of Human Genetics, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA.
Ann N Y Acad Sci. 2013 Apr;1281(1):178-90. doi: 10.1111/nyas.12020. Epub 2013 Jan 29.
It has long been known that there is a genetic component to obesity, and that characterizing this underlying factor would likely offer the possibility of better intervention in the future. Monogenic obesity has proved to be relatively straightforward, with a combination of linkage analysis and mouse models facilitating the identification of multiple genes. In contrast, genome-wide association studies have successfully revealed a variety of genetic loci associated with the more common form of obesity, allowing for very strong consensus on the underlying genetic architecture of the phenotype for the first time. Although a number of significant findings have been made, it appears that very little of the apparent heritability of body mass index has actually been explained to date. New approaches for data analyses and advances in technology will be required to uncover the elusive missing heritability, and to aid in the identification of the key causative genetic underpinnings of obesity.
长期以来,人们一直知道肥胖与遗传因素有关,而阐明这一潜在因素可能为未来的更好干预提供可能性。单基因肥胖已被证明相对简单,通过连锁分析和小鼠模型的组合,有助于鉴定多种基因。相比之下,全基因组关联研究成功揭示了多种与更为常见的肥胖形式相关的遗传位点,首次允许对表型的潜在遗传结构达成非常强烈的共识。尽管已经取得了一些重要的发现,但迄今为止,似乎只有很少一部分体重指数的明显遗传性得到了真正的解释。需要新的数据分析方法和技术进步来揭示难以捉摸的遗传缺失,并帮助确定肥胖的关键致病遗传基础。