From modeling to measurement: developmental trends in genetic influence on adiposity in childhood.
From modeling to measurement: developmental trends in genetic influence on adiposity in childhood.
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作者：
Llewellyn, C. H.;Trzaskowski, M.;Plomin, R.;Wardle, J.
考虑到长期暴露在环境影响下，儿童时期BMI遗传能力增加的证据似乎是矛盾的。基因组数据被用来提供遗传影响在发育过程中增加的直接证据。在双胞胎早期发展研究中，计算了2556对双胞胎在4岁和10岁时的BMI标准偏差评分（BMI- sds）。双生子分析估计了BMI-SDS在每个年龄段的遗传力和纵向遗传相关性。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）确定了每个年龄的dna遗传力和纵向基因组相关性。使用28个与肥胖相关的单核苷酸多态性（snp）来评估每个年龄段与多基因肥胖风险评分（PRS）的关联，并通过自举来检验方差增加的显著性。双胞胎估计遗传率从4岁（0.43;95% CI: 0.35-0.53）增加到10岁（0.82;0.74-0.88）。gcta估计的遗传力从4（0.20;- 0.21至0.61）时的不显著变为10（0.29;0.01-0.57）时的显著。双胞胎（0.58）和GCTA（0.66）的纵向遗传相关性相似。相同的PRS解释了10年比4年更多的方差（R2 Δ：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，但遗传对儿童时期肥胖的影响越来越大。
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 (R2 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.
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Silventoinen, Karri;Bartels, Meike;Boomsma, Dorret I.
通讯作者：
Boomsma, Dorret I.