Fall Tove, Mendelson Michael, Speliotes Elizabeth K
Department of Medical Sciences and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
The Framingham Heart Study, Framingham, Massachusetts; Population Sciences Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.
Gastroenterology. 2017 May;152(7):1695-1706. doi: 10.1053/j.gastro.2017.01.054. Epub 2017 Feb 15.
Obesity is a heritable trait that contributes to substantial global morbidity and mortality. Here, we summarize findings from the past decade of genetic and epigenetic research focused on unravelling the underpinnings of adiposity. More than 140 genetic regions now are known to influence adiposity traits. The genetics of general adiposity, as measured by body mass index, and that of abdominal obesity, as measured by waist-to-hip ratio, have distinct biological backgrounds. Gene expression associated with general adiposity is enriched in the nervous system. In contrast, genes associated with abdominal adiposity function in adipose tissue. Recent population-based epigenetic analyses have highlighted additional distinct loci. We discuss how associated genetic variants can lead to understanding causal mechanisms, and to disentangling reverse causation in epigenetic analyses. Discoveries emerging from population genomics are identifying new disease markers and potential novel drug targets to better define and combat obesity and related diseases.
肥胖是一种可遗传的特征，导致全球大量发病和死亡。在此，我们总结过去十年专注于揭示肥胖基础的遗传和表观遗传学研究结果。目前已知超过140个基因区域影响肥胖特征。通过体重指数衡量的全身肥胖遗传学，以及通过腰臀比衡量的腹部肥胖遗传学，具有不同的生物学背景。与全身肥胖相关的基因表达在神经系统中富集。相比之下，与腹部肥胖相关的基因在脂肪组织中发挥作用。最近基于人群的表观遗传学分析突出了其他不同的基因座。我们讨论相关的基因变异如何有助于理解因果机制，并在表观遗传学分析中理清反向因果关系。群体基因组学中出现的发现正在识别新的疾病标志物和潜在的新型药物靶点，以更好地界定和对抗肥胖及相关疾病。
