Mercader Josep M, Florez Jose C
Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, United States.
Diabetes Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States.
Front Public Health. 2017 Dec 11;5:329. doi: 10.3389/fpubh.2017.00329. eCollection 2017.
Type 2 diabetes (T2D) affects 415 million people worldwide, and has a much higher prevalence in Hispanics (16.9%), compared to non-Hispanic whites (10.2%). Genome-wide association studies and whole-genome and whole-exome sequencing studies have discovered more than 100 genetic regions associated with modified risk for T2D. However, the identified genetic factors explain a very small fraction of the estimated heritability. Until recently, little attention has been put in studying other non European populations that suffer from a higher burden of T2D, such as Hispanics/Latinos. In the past few years, genetic studies in Hispanic populations have started to provide new insights into the genetic architecture of T2D in this ancestry group. Of note, several genetic variants that are absent or very rare in non-Hispanic populations but more common in Hispanics have shown from moderate to strong association with T2D and have provided new insights into the biology of T2D, which may be ultimately useful for developing novel therapeutic strategies applicable to all populations. Studying diverse populations can also improve the ability to find the causal variants in known T2D by a multi-ancestry fine-mapping approach, which leverages the different patterns of linkage disequilibrium between the causal and the ascertained genetic variants. In this mini-review, we summarize the main genetic findings discovered in Hispanics and discuss the limitations and challenges of performing genetic studies in these populations. Finally, we present possible next steps to make studies in Latino populations more valuable in providing a deeper understanding of T2D and anticipate their future application to the development of predictive and preventive medicine and personalized therapies.
2型糖尿病(T2D)影响着全球4.15亿人,与非西班牙裔白人(10.2%)相比,西班牙裔的患病率要高得多(16.9%)。全基因组关联研究以及全基因组和全外显子测序研究已经发现了100多个与T2D风险改变相关的基因区域。然而,已确定的遗传因素仅解释了估计遗传力的很小一部分。直到最近,对于患有更高T2D负担的其他非欧洲人群,如西班牙裔/拉丁裔人群的研究仍很少受到关注。在过去几年中,针对西班牙裔人群的遗传学研究开始为本族裔群体中T2D的遗传结构提供新的见解。值得注意的是,一些在非西班牙裔人群中不存在或非常罕见但在西班牙裔中更常见的基因变异,已显示出与T2D存在中度至强关联,并为T2D生物学提供了新的见解,这最终可能有助于开发适用于所有人群的新型治疗策略。通过多祖先精细定位方法研究不同人群,还可以提高在已知T2D中找到因果变异的能力,该方法利用了因果变异和已确定的遗传变异之间不同的连锁不平衡模式。在本综述中,我们总结了在西班牙裔人群中发现的主要遗传学研究结果,并讨论了在这些人群中进行遗传学研究的局限性和挑战。最后,我们提出了可能的后续步骤,以使拉丁裔人群的研究在更深入理解T2D方面更有价值,并预期它们未来在预测性和预防性医学以及个性化治疗发展中的应用。