MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
Curr Diab Rep. 2018 May 19;18(7):40. doi: 10.1007/s11892-018-1009-1.
Causality has been demonstrated for few of the many putative risk factors for type 2 diabetes (T2D) emerging from observational epidemiology. Genetic approaches are increasingly being used to infer causality, and in this review, we discuss how genetic discoveries have shaped our understanding of the causal role of factors associated with T2D.
Genetic discoveries have led to the identification of novel potential aetiological factors of T2D, including the protective role of peripheral fat storage capacity and specific metabolic pathways, such as the branched-chain amino acid breakdown. Consideration of specific genetic mechanisms contributing to overall lipid levels has suggested that distinct physiological processes influencing lipid levels may influence diabetes risk differentially. Genetic approaches have also been used to investigate the role of T2D and related metabolic traits as causal risk factors for other disease outcomes, such as cancer, but comprehensive studies are lacking. Genome-wide association studies of T2D and metabolic traits coupled with high-throughput molecular phenotyping and in-depth characterisation and follow-up of individual loci have provided better understanding of aetiological factors contributing to T2D.
从观察性流行病学中出现的众多 2 型糖尿病（T2D）推测性风险因素中，有少数已证实其因果关系。遗传方法越来越多地被用于推断因果关系，在这篇综述中，我们讨论了遗传发现如何改变我们对与 T2D 相关的因素的因果作用的理解。
遗传发现导致了 T2D 的新的潜在病因因素的确定，包括外周脂肪储存能力和特定代谢途径（如支链氨基酸分解）的保护作用。考虑到导致总脂质水平的特定遗传机制表明，影响脂质水平的不同生理过程可能会以不同的方式影响糖尿病风险。遗传方法也被用于研究 T2D 和相关代谢特征作为其他疾病结果（如癌症）的因果风险因素的作用，但全面的研究还很缺乏。T2D 和代谢特征的全基因组关联研究，结合高通量分子表型以及对个体基因座的深入特征描述和随访，为导致 T2D 的病因因素提供了更好的理解。
