Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge, UK.
Expert Rev Mol Med. 2010 Feb 26;12:e7. doi: 10.1017/S1462399410001389.
The prevalence of obesity and diabetes, which are heritable traits that arise from the interactions of multiple genes and lifestyle factors, continues to rise worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past 15 years, candidate gene and genome-wide linkage studies have been the main genetic epidemiological approaches to identify genetic loci for obesity and diabetes, yet progress has been slow and success limited. The genome-wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries. Genome-wide association is a hypothesis-generating approach that aims to identify new loci associated with the disease or trait of interest. So far, three waves of large-scale genome-wide association studies have identified 19 loci for common obesity and 18 for common type 2 diabetes. Although the combined contribution of these loci to the variation in obesity and diabetes risk is small and their predictive value is typically low, these recently identified loci are set to substantially improve our insights into the pathophysiology of obesity and diabetes. This will require integration of genetic epidemiological methods with functional genomics and proteomics. However, the use of these novel insights for genetic screening and personalised treatment lies some way off in the future.
肥胖症和糖尿病的患病率在全球范围内持续上升,这些疾病是由多个基因和生活方式因素相互作用引起的遗传性特征,它们会导致严重的健康问题,并给社会带来巨大的经济负担。在过去的 15 年中,候选基因和全基因组连锁研究一直是识别肥胖症和糖尿病遗传基因座的主要遗传流行病学方法,但进展缓慢,成功有限。近年来出现的全基因组关联方法极大地改变了基因发现的速度。全基因组关联是一种产生假设的方法,旨在识别与疾病或感兴趣的特征相关的新基因座。到目前为止,三波大规模全基因组关联研究已经确定了 19 个常见肥胖症和 18 个常见 2 型糖尿病的基因座。尽管这些基因座对肥胖和糖尿病风险的变异的综合贡献很小,并且它们的预测值通常较低,但这些最近确定的基因座有望大大提高我们对肥胖症和糖尿病病理生理学的认识。这将需要将遗传流行病学方法与功能基因组学和蛋白质组学相结合。然而,将这些新的见解用于遗传筛查和个性化治疗还有很长的路要走。