Waalen Jill
The Scripps Research Institute and the Scripps Translational Science Institute, La Jolla, California.
Transl Res. 2014 Oct;164(4):293-301. doi: 10.1016/j.trsl.2014.05.010. Epub 2014 May 23.
The heritability of obesity has long been appreciated and the genetics of obesity has been the focus of intensive study for decades. Early studies elucidating genetic factors involved in rare monogenic and syndromic forms of extreme obesity focused attention on dysfunction of hypothalamic leptin-related pathways in the control of food intake as a major contributor. Subsequent genome-wide association studies of common genetic variants identified novel loci that are involved in more common forms of obesity across populations of diverse ethnicities and ages. The subsequent search for factors contributing to the heritability of obesity not explained by these 2 approaches ("missing heritability") has revealed additional rare variants, copy number variants, and epigenetic changes that contribute. Although clinical applications of these findings have been limited to date, the increasing understanding of the interplay of these genetic factors with environmental conditions, such as the increased availability of high calorie foods and decreased energy expenditure of sedentary lifestyles, promises to accelerate the translation of genetic findings into more successful preventive and therapeutic interventions.
肥胖的遗传性早已为人所知，几十年来肥胖遗传学一直是深入研究的焦点。早期阐明罕见单基因和综合征性极端肥胖所涉及遗传因素的研究，将注意力集中在下丘脑瘦素相关通路在控制食物摄入方面的功能障碍是一个主要因素。随后对常见遗传变异的全基因组关联研究确定了新的基因座，这些基因座涉及不同种族和年龄人群中更常见的肥胖形式。随后对这两种方法未解释的肥胖遗传性因素（“缺失遗传性”）的研究发现了其他起作用的罕见变异、拷贝数变异和表观遗传变化。尽管这些发现的临床应用迄今有限，但对这些遗传因素与环境条件（如高热量食物供应增加和久坐生活方式导致的能量消耗减少）相互作用的日益了解，有望加速将遗传研究结果转化为更成功的预防和治疗干预措施。
