Llewellyn C H, Trzaskowski M, Plomin R, Wardle J
Health Behavior Research Center, Department of Epidemiology & Public Health, University College London, UK; MRC Social, Genetic and Developmental Psychiatry Center, Institute of Psychiatry, King's College London, UK.
Obesity (Silver Spring). 2014 Jul;22(7):1756-61. doi: 10.1002/oby.20756. Epub 2014 Apr 24.
Evidence of increasing heritability of BMI over childhood can seem paradoxical given longer exposure to environmental influences. Genomic data were used to provide direct evidence of developmental increases in genetic influence.
BMI standard deviation scores (BMI-SDS) at ages 4 and 10 were calculated for 2,556 twin pairs in the Twins Early Development Study. Twin analyses estimated heritability of BMI-SDS at each age and the longitudinal genetic correlation. One randomly selected twin per pair was genotyped. Genome-wide complex trait analysis (GCTA) determined DNA-based heritability at each age and the longitudinal genomic correlation. Associations with a polygenic obesity risk score (PRS) using 28 obesity-related single nucleotide polymorphisms (SNPs) were assessed at each age, with bootstrapping to test the significance of the increase in variance explained.
Twin-estimated heritability increased from age 4 (0.43; 95% CI: 0.35-0.53) to 10 (0.82; 0.74-0.88). GCTA-estimated heritability went from non-significant at 4 (0.20; -0.21 to 0.61) to significant at 10 (0.29; 0.01-0.57). Longitudinal genetic correlations derived from twins (0.58) and GCTA (0.66) were similar. The same PRS explained more variance at 10 than 4 years (R(2) Δ:0.024; 0.002-0.078).
GCTA and PRS findings confirm twin-based results suggesting increasing genetic influence on adiposity during childhood despite substantial genetic stability.
鉴于儿童期暴露于环境影响的时间更长，BMI遗传力增加的证据似乎自相矛盾。本研究利用基因组数据直接证明遗传影响在发育过程中的增加。
在双胞胎早期发育研究中，计算了2556对双胞胎在4岁和10岁时的BMI标准差得分（BMI-SDS）。双胞胎分析估计了各年龄BMI-SDS的遗传力以及纵向遗传相关性。每对双胞胎中随机选择一个进行基因分型。全基因组复杂性状分析（GCTA）确定了各年龄基于DNA的遗传力以及纵向基因组相关性。在各年龄评估了与使用28个肥胖相关单核苷酸多态性（SNP）的多基因肥胖风险评分（PRS）的关联，并通过自抽样检验所解释方差增加的显著性。
双胞胎估计的遗传力从4岁时的0.43（95%CI：0.35-0.53）增加到10岁时的0.82（0.74-0.88）。GCTA估计的遗传力从4岁时不显著（0.20；-0.21至0.61）变为10岁时显著（0.29；0.01-0.57）。来自双胞胎（0.58）和GCTA（0.66）的纵向遗传相关性相似。相同的PRS在10岁时比4岁时解释了更多的方差（R(2)变化：0.024；0.002-0.078）。
GCTA和PRS的研究结果证实了基于双胞胎的结果，表明尽管遗传稳定性较高，但儿童期遗传对肥胖的影响仍在增加。
