Polygenic Risk, Rapid Childhood Growth, and the Development of Obesity Evidence From a 4-Decade Longitudinal Study
Polygenic Risk, Rapid Childhood Growth, and the Development of Obesity Evidence From a 4-Decade Longitudinal Study
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DOI：
10.1001/archpediatrics.2012.131
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发表时间：
2012-06-01
影响因子：
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通讯作者：
Caspi, Avshalom
中科院分区：
文献类型：
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作者：
Belsky, Daniel W.;Moffitt, Terrie E.;Caspi, Avshalom
目的：为了测试全基因组关联研究中确定的基因组位点如何影响肥胖症的发展，设计：一项38年的前瞻性纵向研究，一个有代表性的出生队列，设置：达尼丁多学科健康与发展研究，达尼丁，新西兰，参与者：1037名男性和女性研究成员，主要暴露：我们评估了多位点遗传风险评分的遗传风险。遗传风险评分由肥胖相关表型的全基因组关联研究中鉴定的单核苷酸多态性组成。我们从研究成员11岁时收集的父母体重指数数据评估家族史。主要结果测量：体重指数生长曲线、肥胖的发育表型和成人肥胖结果是从出生时的人体测量评估和随后12次到38岁的面对面访谈中定义的。具有较高遗传风险分数的个体更有可能在成年后患上慢性肥胖症。遗传风险首先表现为儿童早期的快速增长。遗传风险与出生体重无关。出生后，遗传风险较高的儿童体重增加更快，更早达到肥胖反弹，体重指数更高。反过来，这些发育表型预测了成人肥胖，介导了成人肥胖风险的遗传效应的一半。与生长和肥胖风险的遗传关联是独立的家族史，表明遗传风险评分可以提供新的信息，临床医生。结论：遗传变异与肥胖风险的运作，在一定程度上，通过加速生长在出生后的早期儿童年。病因学研究和预防战略应针对幼儿期，以解决肥胖症的流行。
Objective: To test how genomic loci identified in genome-wide association studies influence the development of obesity.Design: A 38-year prospective longitudinal study of a representative birth cohort.Setting: The Dunedin Multidisciplinary Health and Development Study, Dunedin, New Zealand.Participants: One thousand thirty-seven male and female study members.Main Exposures: We assessed genetic risk with a multilocus genetic risk score. The genetic risk score was composed of single-nucleotide polymorphisms identified in genome-wide association studies of obesity-related phenotypes. We assessed family history from parent body mass index data collected when study members were 11 years of age.Main Outcome Measures: Body mass index growth curves, developmental phenotypes of obesity, and adult obesity outcomes were defined from anthropometric assessments at birth and at 12 subsequent in-person interviews through 38 years of age.Results: Individuals with higher genetic risk scores were more likely to be chronically obese in adulthood. Genetic risk first manifested as rapid growth during early childhood. Genetic risk was unrelated to birth weight. After birth, children at higher genetic risk gained weight more rapidly and reached adiposity rebound earlier and at a higher body mass index. In turn, these developmental phenotypes predicted adult obesity, mediating about half the genetic effect on adult obesity risk. Genetic associations with growth and obesity risk were independent of family history, indicating that the genetic risk score could provide novel information to clinicians.Conclusions: Genetic variation linked with obesity risk operates, in part, through accelerating growth in the early childhood years after birth. Etiological research and prevention strategies should target early childhood to address the obesity epidemic.