GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI
GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI
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DOI：
10.1126/sciadv.aaw3095
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发表时间：
2019-09-01
期刊：
影响因子：
13.6
通讯作者：
Jarvelin, Marjo-Riitta
中科院分区：
文献类型：
--
作者：
Alves, Alexessander Couto;De Silva, N. Maneka G.;Jarvelin, Marjo-Riitta
儿童早期生长模式与成人健康有关，但遗传因素和所涉及的发育阶段尚未完全了解。在这里，我们将联合收割机全基因组关联研究与纵向生长性状建模相结合，研究婴儿和儿童生长的遗传学，然后进行功能、途径、遗传相关性、风险评分和共定位分析，以确定这些性状的发育时间、分子途径和遗传决定因素与成人健康的遗传决定因素如何重叠。我们发现儿童和成人身体质量指数（BMI）的遗传学之间存在强烈的重叠，与成人BMI相关的变异早在4至6岁时就开始起作用。然而，我们证明了一个完全不同的基因组成的峰值体重指数在婴儿期，在LEPR/LEPROT基因座的变化的影响。这些发现表明，不同的遗传因素控制着婴儿和儿童的BMI。鉴于肥胖症的流行，这些发现对于告知预防策略的时机和目标非常重要。
Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.