Satiety mechanisms in genetic risk of obesity.
Satiety mechanisms in genetic risk of obesity.
复制标题
DOI：
10.1001/jamapediatrics.2013.4944
复制
发表时间：
2014-04
期刊：
影响因子：
26.1
通讯作者：
Wardle, Jane
中科院分区：
文献类型：
--
作者：
Llewellyn, Clare H.;Trzaskowski, Maciej;van Jaarsveld, Cornelia H. M.;Plomin, Robert;Wardle, Jane
更好地了解肥胖的病因是临床的首要任务。肥胖具有高度遗传性，并且正在鉴定特定基因。发现肥胖相关基因影响体重的机制将有助于确定新的干预目标。一种潜在的机制是饱腹感反应。缺乏饱腹感是许多单基因肥胖症的特征，而较低的饱腹感反应性与人群样本中的体重增加有关。我们测试了这样的假设：饱腹感反应是与儿童肥胖遗传倾向相关的中间行为表型。横断面观察研究。基于人口的 1994 年至 1996 年出生的双胞胎队列（双胞胎早期发育研究）。 2258 名无关儿童（53% 为女性；平均年龄：9.9 岁，SD：0.84）；从每对双胞胎中随机选择一个。肥胖的遗传倾向。我们创建了一个多基因风险评分 (PRS)，其中包含在肥胖相关全基因组关联研究的荟萃分析中鉴定出的 28 个常见的肥胖相关单核苷酸多态性。饱腹感反应性以标准心理测量量表（儿童饮食行为问卷）为索引。 BMI 标准差分数 (BMI-SDS) 和腰围-SDS 使用 1990 年英国参考数据，根据家长报告的儿童人体测量数据计算得出。 2258 名儿童获得了有关饱腹感反应、人体测量学和基因型的信息。我们研究了 PRS、肥胖和饱腹感反应之间的关联。 PRS 与饱腹感反应呈负相关（β，-0.060；95% CI，-0.019 至 -0.101），与肥胖呈正相关（BMI-SDS：β，0.177；95% CI，0.136 至 0.218；腰围-SDS：β，0.167；95% CI，0.126 至0.208），并且 PRS 中前 25% 的儿童超重的比例高于后 25% 的儿童（分别为 18.5% 和 7.2%；OR，2.90；95% CI，1.98 至 4.25）。 PRS 和肥胖之间的关联显着由饱腹感反应介导（BMI-SDS：P = 0.006；腰围-SDS：P = 0.005）。这些结果支持这样的假设：低饱腹感反应是遗传倾向导致食物丰富的环境中体重增加的机制之一。增强饱腹感反应的策略可以帮助预防遗传风险儿童的体重增加。
A better understanding of the etiology of obesity is a clinical priority. Obesity is highly heritable and specific genes are being identified. Discovering the mechanisms through which obesity-related genes influence weight would help pinpoint novel targets for intervention. One potential mechanism is satiety responsiveness. Lack of satiety characterizes many monogenic obesity disorders, and lower satiety responsiveness is linked with weight gain in population samples. We tested the hypothesis that satiety responsiveness is an intermediate behavioral phenotype associated with genetic predisposition to obesity in children. Cross-sectional observational study. Population-based cohort of twins born 1994–1996 (Twins Early Development Study). 2258 unrelated children (53% female; mean age: 9.9 years, SD: 0.84); one randomly selected from each twin pair. Genetic predisposition to obesity. We created a polygenic risk score (PRS) comprising 28 common obesity-related single nucleotide polymorphisms identified in a meta-analysis of obesity-related genome-wide association studies. Satiety responsiveness was indexed with a standard psychometric scale (the Child Eating Behavior Questionnaire). BMI standard deviation scores (BMI-SDS) and waist-SDS, using 1990 UK reference data, were calculated from parent-reported anthropometric data for the child. Information on satiety responsiveness, anthropometrics and genotype were available for 2258 children. We examined associations between the PRS, adiposity and satiety responsiveness. The PRS was negatively related to satiety responsiveness (beta, −0.060; 95% CI, −0.019 to −0.101), and positively related to adiposity (BMI-SDS: beta, 0.177; 95% CI, 0.136 to 0.218; waist-SDS: beta, 0.167; 95% CI, 0.126 to 0.208), and more children in the top 25% of the PRS were overweight than in the lowest 25% (18.5% versus 7.2%, respectively; OR, 2.90; 95% CI, 1.98 to 4.25). Associations between the PRS and adiposity were significantly mediated by satiety responsiveness (BMI-SDS: P = 0.006; waist-SDS: P = 0.005). These results support the hypothesis that low satiety responsiveness is one of the mechanisms through which genetic predisposition leads to weight gain in an environment rich with food. Strategies to enhance satiety responsiveness could help prevent weight gain in genetically at-risk children.
登录
查看更多内容
影响因子：
158.5
作者：
Cecil, Joanne E.;Tavendale, Roger;Palmer, Colin N. A.
通讯作者：
Palmer, Colin N. A.
影响因子：
7.1
作者：
Llewellyn, Clare H.;van Jaarsveld, Cornelia H. M.;Wardle, Jane
通讯作者：
Wardle, Jane
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Lee, James C.;Lees, Charles W.;Prescott, Natalie J.;Anderson, Carl A.;Phillips, Anne;Wesley, Emma;Parnell, Kirstie;Zhang, Hu;Drummond, Hazel;Nimmo, Elaine R.;Massey, Dunecan;Blaszczyk, Kasia;Elliott, Timothy;Cotterill, Lynn;Dallal, Helen;Lobo, Alan J.;Mowat, Craig;Sanderson, Jeremy D.;Jewell, Derek P.;Newman, William G.;Edwards, Cathryn;Ahmad, Tariq;Mansfield, John C.;Satsangi, Jack;Parkes, Miles;Mathew, Christopher G.;Donnelly, Peter;Peltonen, Leena;Blackwell, Jenefer M.;Bramon, Elvira;Brown, Matthew A.;Casas, Juan P.;Corvin, Aiden;Craddock, Nicholas;Deloukas, Panos;Duncanson, Audrey;Jankowski, Janusz;Markus, Hugh S.;McCarthy, Mark I.;Palmer, Colin N. A.;Plomin, Robert;Rautanen, Anna;Sawcer, Stephen J.;Samani, Nilesh;Trembath, Richard C.;Viswanathan, Ananth C.;Wood, Nicholas;Spencer, Chris C. A.;Bellenguez, Celine;Davison, Daniel;Freeman, Colin;Strange, Amy;Langford, Cordelia;Hunt, Sarah E.;Edkins, Sarah;Gwilliam, Rhian;Blackburn, Hannah;Bumpstead, Suzannah J.;Dronov, Serge;Gillman, Matthew;Gray, Emma;Hammond, Naomi;Jayakumar, Alagurevathi;McCann, Owen T.;Liddle, Jennifer;Perez, Marc L.;Potter, Simon C.;Ravindrarajah, Radhi;Ricketts, Michelle;Waller, Matthew;Weston, Paul;Widaa, Sara;Whittaker, Pamela;Attwood, Antony P.;Stephens, Jonathan;Sambrook, Jennifer;Ouwehand, Willem H.;McArdle, Wendy L.;Ring, Susan M.;Strachan, David P.
通讯作者：
Strachan, David P.
影响因子：
5.4
作者：
Carnell, Susan;Wardle, Jane
通讯作者：
Wardle, Jane