MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
Am J Clin Nutr. 2012 May;95(5):1150-6. doi: 10.3945/ajcn.111.027870. Epub 2012 Mar 28.
Longitudinal growth associations with genetic variants identified for adult BMI may provide insights into the timing of obesity susceptibility.
The objective was to explore associations of known BMI loci with measures of body size from birth to adulthood.
A total of 2537 individuals from a longitudinal British birth cohort were genotyped for 11 genetic variants robustly associated with adult BMI (in/near FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, ETV5, SEC16B, SH2B1, and MTCH2). We derived an obesity-risk-allele score, comprising the sum of BMI-increasing alleles in each individual, and examined this for an association with birth weight and repeated measures of weight, height, and BMI SD scores (SDS) at 11 time points between ages 2 and 53 y.
The obesity-risk-allele score showed borderline significant association with birth weight (0.019 SDS/allele; P = 0.05) and was more clearly associated with higher weight and BMI at all time points between ages 2 and 53 y; the strongest associations with weight occurred at ages 11 and 20 y (both 0.056 SDS/allele). In longitudinal analyses, the score was positively associated with weight gain only between birth and 11 y (0.003 SDS/allele per year; 95% CI: 0.001, 0.004; P = 0.001). The risk-allele score was associated with taller height at 7 y (0.031 SDS/allele; P = 0.002) and greater height gains between 2 and 7 y (0.007 SDS/allele per year; P < 0.001), but not with adult height (P = 0.5).
The combined effect of adult obesity susceptibility variants on weight gain was confined to childhood. These variants conferred a faster tempo of height growth that was evident before the pubertal years.
与成人 BMI 相关的遗传变异与纵向生长的关联，可能有助于深入了解肥胖易感性的时间。
本研究旨在探索已知 BMI 相关基因座与从出生到成年的身体大小测量值之间的关联。
对来自英国一项纵向出生队列的 2537 名个体进行了 11 种与成人 BMI 密切相关的遗传变异（FTO、MC4R、TMEM18、GNPDA2、KCTD15、NEGR1、BDNF、ETV5、SEC16B、SH2B1 和 MTCH2 内或附近）的基因分型。我们得出了一个肥胖风险等位基因评分，由每个个体中 BMI 增加等位基因的总和组成，并在年龄为 2 至 53 岁之间的 11 个时间点上，检查该评分与出生体重以及体重、身高和 BMI 标准差评分（SDS）的重复测量值之间的关联。
肥胖风险等位基因评分与出生体重呈边缘显著相关（0.019 SDS/等位基因；P = 0.05），并且与年龄为 2 至 53 岁之间所有时间点的更高体重和 BMI 更明显相关；与体重最强的关联发生在 11 岁和 20 岁（均为 0.056 SDS/等位基因）。在纵向分析中，该评分仅与出生至 11 岁之间的体重增加呈正相关（每年 0.003 SDS/等位基因；95%CI：0.001，0.004；P = 0.001）。风险等位基因评分与 7 岁时的身高较高（0.031 SDS/等位基因；P = 0.002）和 2 至 7 岁之间的身高增长较大（每年 0.007 SDS/等位基因；P < 0.001）相关，但与成人身高无关（P = 0.5）。
成人肥胖易感性变异对体重增加的综合影响仅限于儿童时期。这些变异赋予了在青春期之前就明显存在的更高的身高增长速度。
