从出生到成年的体重和肥胖轨迹的多基因预测。
Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood.
机构信息
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Cardiology, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
出版信息
Cell. 2019 Apr 18;177(3):587-596.e9. doi: 10.1016/j.cell.2019.03.028.
Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment.
严重肥胖是一种迅速蔓延的全球健康威胁。尽管肥胖通常归因于不健康的生活方式选择或环境因素，但已知肥胖具有遗传性和高度多基因性；大多数遗传易感性与许多常见 DNA 变异的累积效应有关。在这里，我们开发并验证了一种由 210 万个常见变异组成的新多基因预测因子，以量化这种易感性，并在从中年到出生的 30 多万人中测试该预测因子。在中年人群中，我们观察到体重呈 13 公斤梯度分布，在多基因评分十分位数中严重肥胖的风险呈 25 倍梯度分布。在一个纵向出生队列中，我们注意到评分十分位数之间的出生体重差异极小，但在儿童早期出现了显著的梯度，到 18 岁时达到 12 公斤。这种量化肥胖遗传易感性的新方法为临床预防和机制评估提供了新的机会。
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