Characterization of the genetic architecture of infant and early childhood body mass index
Characterization of the genetic architecture of infant and early childhood body mass index
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DOI：
10.1038/s42255-022-00549-1
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发表时间：
2022-03-21
影响因子：
20.8
通讯作者：
Johansson, Stefan
中科院分区：
文献类型：
--
作者：
Helgeland, Oyvind;Vaudel, Marc;Johansson, Stefan
Helgeland等人描述了与儿童早期体重指数相关的遗传位点，强调了单基因肥胖、食欲调节和能量消耗相关基因的作用，其中许多基因显示出年龄特异性关联模式。儿童早期肥胖是一个日益增长的全球性问题;然而，常见遗传变异对婴儿和儿童体重发展的作用尚不清楚。在这里，我们确定了46个位点与特定年龄的幼儿体重指数相关，匹配不同的儿童生长阶段，并代表四个主要的轨迹模式。我们在挪威母亲，父亲和儿童队列研究中对28，681名儿童及其父母（27，088名母亲和26，239名父亲）从出生到8岁的12个时间点进行了全基因组关联研究。单基因肥胖基因在已确定的基因座附近过度表达，LEPR、GLP 1 R、PCSK 1和KLF 14附近的几个复杂关联信号指向影响早期生活中瘦素-黑皮质素系统的常见变异的主要影响，提供了与推定治疗策略的联系。我们还展示了不同的多基因风险评分如何通过儿童早期生长从出生过渡到成年。总之，我们的研究结果提供了一个不断变化的遗传景观维持儿童早期生长的细粒度表征。
Helgeland et al. characterize genetic loci associated with early childhood body mass index, highlighting roles of genes involved in monogenic obesity, appetite regulation and energy expenditure, many of which show age-specific association patterns.Early childhood obesity is a growing global concern; however, the role of common genetic variation on infant and child weight development is unclear. Here, we identify 46 loci associated with early childhood body mass index at specific ages, matching different child growth phases, and representing four major trajectory patterns. We perform genome-wide association studies across 12 time points from birth to 8 years in 28,681 children and their parents (27,088 mothers and 26,239 fathers) in the Norwegian Mother, Father and Child Cohort Study. Monogenic obesity genes are overrepresented near identified loci, and several complex association signals near LEPR, GLP1R, PCSK1 and KLF14 point towards a major influence for common variation affecting the leptin-melanocortin system in early life, providing a link to putative treatment strategies. We also demonstrate how different polygenic risk scores transition from birth to adult profiles through early child growth. In conclusion, our results offer a fine-grained characterization of a changing genetic landscape sustaining early childhood growth.