Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Lund University, CRC, Skåne University Hospital SUS, SE-205 02 Malmö, Sweden.
Finnish Institute of Molecular Medicine (FIMM), Helsinki University, Helsinki 00014, Finland.
Genes (Basel). 2015 Mar 12;6(1):87-123. doi: 10.3390/genes6010087.
Type 2 diabetes (T2D) is a complex disease that is caused by a complex interplay between genetic, epigenetic and environmental factors. While the major environmental factors, diet and activity level, are well known, identification of the genetic factors has been a challenge. However, recent years have seen an explosion of genetic variants in risk and protection of T2D due to the technical development that has allowed genome-wide association studies and next-generation sequencing. Today, more than 120 variants have been convincingly replicated for association with T2D and many more with diabetes-related traits. Still, these variants only explain a small proportion of the total heritability of T2D. In this review, we address the possibilities to elucidate the genetic landscape of T2D as well as discuss pitfalls with current strategies to identify the elusive unknown heritability including the possibility that our definition of diabetes and its subgroups is imprecise and thereby makes the identification of genetic causes difficult.
2 型糖尿病(T2D)是一种复杂的疾病,由遗传、表观遗传和环境因素之间的复杂相互作用引起。虽然主要的环境因素,如饮食和活动水平,是众所周知的,但遗传因素的确定一直是一个挑战。然而,近年来由于技术的发展,全基因组关联研究和下一代测序技术使得 T2D 的风险和保护的遗传变异大量涌现。如今,已经有超过 120 个变异被令人信服地复制与 T2D 相关,还有更多的与糖尿病相关的特征相关。尽管如此,这些变异只解释了 T2D 总遗传率的一小部分。在这篇综述中,我们探讨了阐明 T2D 遗传景观的可能性,并讨论了当前识别难以捉摸的未知遗传率的策略所存在的陷阱,包括我们对糖尿病及其亚组的定义不精确,从而使遗传原因的识别变得困难的可能性。