Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108, Freiburg, Germany.
Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108, Freiburg, Germany.
Mol Metab. 2018 Aug;14:26-38. doi: 10.1016/j.molmet.2018.05.010. Epub 2018 May 18.
The alarming rise of obesity and its associated comorbidities represents a medical burden and a major global health and economic issue. Understanding etiological mechanisms underpinning susceptibility and therapeutic response is of primary importance. Obesity, diabetes, and metabolic diseases are complex trait disorders with only partial genetic heritability, indicating important roles for environmental programing and epigenetic effects.
We will highlight some of the reasons for the scarce predictability of metabolic diseases. We will outline how genetic variants generate phenotypic variation in disease susceptibility across populations. We will then focus on recent conclusions about epigenetic mechanisms playing a fundamental role in increasing variability and subsequently disease triggering.
Currently, we are unable to predict or mechanistically define how "missing heritability" drives disease. Unravelling this black box of regulatory processes will allow us to move towards a truly personalized and precision medicine.
肥胖及其相关并发症的惊人上升，代表着一种医疗负担，也是一个主要的全球健康和经济问题。了解导致易感性和治疗反应的病因机制至关重要。肥胖、糖尿病和代谢疾病是具有部分遗传遗传性的复杂特征障碍，这表明环境编程和表观遗传效应的重要作用。
我们将强调代谢疾病预测性差的部分原因。我们将概述遗传变异如何在不同人群中产生疾病易感性的表型变异。然后，我们将重点关注最近关于在增加可变性并随后引发疾病方面发挥基础性作用的表观遗传机制的结论。
目前，我们无法预测或从机制上定义“缺失的遗传率”如何驱动疾病。揭示这一调控过程的黑匣子，将使我们能够迈向真正的个性化和精准医学。
