aDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore bKhoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System cSingapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, Singapore.
Curr Opin Pediatr. 2013 Dec;25(6):666-73. doi: 10.1097/MOP.0b013e3283658fba.
Common obesity is widely regarded as a complex, multifactorial trait influenced by the 'obesogenic' environment, sedentary behavior, and genetic susceptibility contributed by common and rare genetic variants. This review describes the recent advances in understanding the role of genetics in obesity.
New susceptibility loci and genetic variants are being uncovered, but the collective effect is relatively small and could not explain most of the BMI heritability. Yet-to-be identified common and rare variants, epistasis, and heritable epigenetic changes may account for part of the 'missing heritability'. Evidence is emerging about the role of epigenetics in determining obesity susceptibility, mediating developmental plasticity, which confers obesity risk from early life experiences. Genetic prediction scores derived from selected genetic variants, and also differential DNA methylation levels and methylation scores, have been shown to correlate with measures of obesity and response to weight loss intervention. Genetic variants, which confer susceptibility to obesity-related morbidities like nonalcoholic fatty liver disease, were also discovered recently.
We can expect discovery of more rare genetic variants with the advent of whole exome and genome sequencing, and also greater understanding of epigenetic mechanisms by which environment influences genetic expression and which mediate the gene-environment interaction.
普通肥胖被广泛认为是一种复杂的多因素特征，受到“致肥胖环境”、久坐行为以及常见和罕见遗传变异共同贡献的遗传易感性的影响。本文综述了遗传因素在肥胖中的作用的最新研究进展。
新的易感基因座和遗传变异正在被发现，但总体效应相对较小，无法解释大部分 BMI 的遗传率。尚未确定的常见和罕见变异、上位性以及可遗传的表观遗传变化可能是“遗传缺失”的一部分原因。关于表观遗传学在决定肥胖易感性、介导发育可塑性方面的作用的证据正在出现，这种可塑性赋予了肥胖的风险，来自于早期生活经历。从选定的遗传变异中得出的遗传预测评分，以及差异 DNA 甲基化水平和甲基化评分，已被证明与肥胖测量和减肥干预的反应相关。最近还发现了一些遗传变异，这些变异使个体易患与肥胖相关的疾病，如非酒精性脂肪肝。
随着外显子组和全基因组测序的出现，我们可以期待发现更多的罕见遗传变异，也可以更好地理解环境影响基因表达的表观遗传机制，以及这些机制介导基因-环境相互作用的方式。
