Justice A E, Chittoor G, Blanco E, Graff M, Wang Y, Albala C, Santos J L, Angel B, Lozoff B, Voruganti V S, North K E, Gahagan S
Biomedical and Translational Informatics, Geisinger, Danville, PA, USA.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Pediatr Obes. 2019 Mar;14(3):e12479. doi: 10.1111/ijpo.12479. Epub 2018 Dec 4.
While the genetic contribution to obesity is well established, few studies have examined how genetic variants influence standardized body mass index Z-score (BMIz) in Hispanics/Latinos, especially across childhood and adolescence.
We estimated the effect of established BMIz loci in Chilean children of the Santiago Longitudinal Study (SLS).
We examined associations with BMIz at age 10 for 15 loci previously identified in European children. For significant loci, we performed association analyses at ages 5 and 16 years, for which we have smaller sample sizes. We tested associations of unweighted genetic risk scores (GRSs) for previously identified tag variants (GRS_EUR) and from the most significant variants in SLS at each locus (GRS_SLS).
We generalized five variants at age 10 (P < 0.05 and directionally consistent), including rs543874 that reached Bonferroni-corrected significance. The effect on BMIz was greatest at age 10 for all significant loci, except FTO, which exhibited an increase in effect from ages 5 to 16. Both GRSs were associated with BMIz (P < 0.0001), but GRS_SLS explained a much greater proportion of the variation (13.63%).
Our results underscore the importance of conducting genetic investigations across life stages and selecting ancestry appropriate tag variants in future studies for disease prediction and clinical evaluation.
虽然遗传因素对肥胖的影响已得到充分证实，但很少有研究探讨基因变异如何影响西班牙裔/拉丁裔人群的标准化体重指数Z评分（BMIz），尤其是在儿童期和青少年期。
我们在圣地亚哥纵向研究（SLS）的智利儿童中估计了已确定的BMIz基因座的影响。
我们研究了先前在欧洲儿童中确定的15个基因座与10岁时BMIz的关联。对于显著的基因座，我们在5岁和16岁时进行了关联分析，这两个年龄段的样本量较小。我们测试了先前确定的标签变体（GRS_EUR）和每个基因座在SLS中最显著变体的未加权遗传风险评分（GRSs）的关联。
我们在10岁时归纳出5个变体（P < 0.05且方向一致），包括达到Bonferroni校正显著性的rs543874。除FTO外，所有显著基因座对BMIz的影响在10岁时最大，FTO从5岁到16岁的影响呈增加趋势。两个GRSs均与BMIz相关（P < 0.0001），但GRS_SLS解释的变异比例要大得多（13.63%）。
我们的结果强调了在未来疾病预测和临床评估研究中，跨生命阶段进行基因研究以及选择适合祖先的标签变体的重要性。
