Bouchard Claude
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Am J Clin Nutr. 2009 May;89(5):1494S-1501S. doi: 10.3945/ajcn.2009.27113C. Epub 2009 Mar 4.
This brief review focuses on the genetic contribution to childhood obesity. Evidence for a genetic component to excess body weight during growth is presented from the perspective of genetic epidemiology studies. Parental obesity is a predictor of childhood excess weight. The familial risk ratio for childhood obesity when a parent is obese reaches >2.5. Birth weight is characterized by a genetic heritability component on the order of 30%, with significant maternal and paternal effects in addition to the newborn genes. About 5% of childhood obesity cases are caused by a defect that impairs function in a gene, and >/=5 of these genes have been uncovered. However, the common forms of childhood obesity seem to result from a predisposition that primarily favors obesogenic behaviors in an obesogenic environment. Candidate gene and genomewide association studies reveal that these obesogenic genes have small effect sizes but that the risk alleles for obesity are quite common in populations. The latter may translate into a highly significant population-attributable risk of obesity. Gene-environment interaction studies suggest that the effects of predisposing genes can be enhanced or diminished by exposure to relevant behaviors. It is possible that the prevalence of childhood obesity is increasing across generations as a result of positive assortative mating with obese husbands and wives contributing more obese offspring than normal-weight parents.
本简要综述聚焦于儿童肥胖的遗传因素。从遗传流行病学研究的角度阐述了生长期间超重存在遗传成分的证据。父母肥胖是儿童超重的一个预测指标。当父母一方肥胖时,儿童肥胖的家族风险比超过2.5。出生体重的遗传度约为30%,除了新生儿自身基因外,还存在显著的母体和父体效应。约5%的儿童肥胖病例是由基因功能缺陷导致的,目前已发现5个以上此类基因。然而,儿童肥胖的常见形式似乎源于一种易感性,这种易感性主要在致胖环境中倾向于致胖行为。候选基因研究和全基因组关联研究表明,这些致胖基因的效应大小较小,但肥胖风险等位基因在人群中相当常见。后者可能转化为肥胖在人群中高度显著的归因风险。基因-环境相互作用研究表明,接触相关行为可增强或减弱易感基因的作用。由于肥胖的夫妻进行正向选型交配,其肥胖后代多于正常体重父母的后代,儿童肥胖的患病率可能会逐代上升。