FACN, Scientific Directorate, Bambino Gesù Pediatric Hospital, Istituto Di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Pediatrics. 2012 Jul;130(1):123-33. doi: 10.1542/peds.2011-2717. Epub 2012 Jun 4.
Onset of obesity has been anticipated at earlier ages, and prevalence has dramatically increased worldwide over the past decades. Epidemic obesity is mainly attributable to modern lifestyle, but family studies prove the significant role of genes in the individual's predisposition to obesity. Advances in genotyping technologies have raised great hope and expectations that genetic testing will pave the way to personalized medicine and that complex traits such as obesity will be prevented even before birth. In the presence of the pressing offer of direct-to-consumer genetic testing services from private companies to estimate the individual's risk for complex phenotypes including obesity, the present review offers pediatricians an update of the state of the art on genomics obesity in childhood. Discrepancies with respect to genomics of adult obesity are discussed. After an appraisal of findings from genome-wide association studies in pediatric populations, the rare variant-common disease hypothesis, the theoretical soil for next-generation sequencing techniques, is discussed as opposite to the common disease-common variant hypothesis. Next-generation sequencing techniques are expected to fill the gap of "missing heritability" of obesity, identifying rare variants associated with the trait and clarifying the role of epigenetics in its heritability. Pediatric obesity emerges as a complex phenotype, modulated by unique gene-environment interactions that occur in periods of life and are "permissive" for the programming of adult obesity. With the advent of next-generation sequencing techniques and advances in the field of exposomics, sensitive and specific tools to predict the obesity risk as early as possible are the challenge for the next decade.
肥胖的发病年龄已经提前，过去几十年来，肥胖的患病率在全球范围内显著增加。肥胖是一种流行疾病，主要归因于现代生活方式，但家族研究证明了基因在个体肥胖易感性方面的重要作用。基因分型技术的进步带来了巨大的希望和期望，即基因检测将为个性化医疗铺平道路，复杂的特征，如肥胖，甚至可以在出生前得到预防。在私营公司提供直接面向消费者的基因检测服务以估计个体包括肥胖在内的复杂表型风险的迫切需求下，本综述为儿科医生提供了儿童肥胖症基因组学最新进展的更新。讨论了与成人肥胖症基因组学的差异。在评估了儿科人群全基因组关联研究的结果后，讨论了罕见变异-常见疾病假说，这是下一代测序技术的理论基础，与常见疾病-常见变异假说相反。下一代测序技术有望填补肥胖症“遗传缺失”的空白，确定与该特征相关的罕见变异，并阐明表观遗传学在其遗传性中的作用。儿科肥胖症是一种复杂的表型，受独特的基因-环境相互作用的调节，这些相互作用发生在生命的各个阶段，并为成年肥胖症的编程提供了“许可”。随着下一代测序技术的出现和暴露组学领域的进步，尽早预测肥胖风险的敏感和特异性工具是未来十年的挑战。
