Adult height variants affect birth length and growth rate in children.
Adult height variants affect birth length and growth rate in children.
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DOI：
10.1093/hmg/ddr309
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发表时间：
2011-10-15
影响因子：
3.5
通讯作者：
Lawlor DA
中科院分区：
文献类型：
--
作者：
Paternoster L;Howe LD;Tilling K;Weedon MN;Freathy RM;Frayling TM;Kemp JP;Smith GD;Timpson NJ;Ring SM;Evans DM;Lawlor DA
之前的研究发现了 180 个与成人身高相关的单核苷酸多态性 (SNP)，解释了约 10% 的变异。这些因素开始影响生长的年龄尚不清楚。我们模拟了这些 SNP 对出生身长和儿童生长的影响。雅芳家长和儿童纵向研究共有 7768 名参与者提供了可用数据。使用混合效应线性样条模型估计 0 至 10 岁的个体生长轨迹，并确定个体 SNP 和等位基因评分的轨迹差异。等位基因评分与出生身长相关（每个“高”等位基因增加 0.026 厘米，SE = 0.003，P = 1 × 10−15，相当于 0.017 SD）。几乎没有证据表明等位基因评分与婴儿早期生长（0-3个月）之间存在关联，但有证据表明等位基因评分与后期生长之间存在关联。这种关联随着每个连续的生长期而变得更强，每个“高”等位基因每月的影响分别为 0.015 SD（3 个月–1 年，SE = 0.004）、0.023 SD（1–3 年，SE = 0.003）和 0.028 SD（3–10 年，SE = 0.003）。到 10 岁时，“高”等位基因≤170 与 ≥191 的个体（顶部和底部各 10%）之间的平均身高差异为 4.7 厘米（0.8 标准差），解释了约 5% 的方差。有证据表明某些 SNP（rs3791675、EFEMP1 和 rs6569648、L3MBTL3）与特定生长期相关，并且有证据支持之前报道的 HHIP 和 SOCS2 SNP 的年龄依赖性影响。与成人身高相关的 SNP 会影响出生身长，并且对从婴儿期晚期到儿童期晚期的生长影响越来越大。到 10 岁时，他们解释的身高差异 (∼5%) 是成人身高差异 (∼10%) 的一半。
Previous studies identified 180 single nucleotide polymorphisms (SNPs) associated with adult height, explaining ∼10% of the variance. The age at which these begin to affect growth is unclear. We modelled the effect of these SNPs on birth length and childhood growth. A total of 7768 participants in the Avon Longitudinal Study of Parents and Children had data available. Individual growth trajectories from 0 to 10 years were estimated using mixed-effects linear spline models and differences in trajectories by individual SNPs and allelic score were determined. The allelic score was associated with birth length (0.026 cm increase per ‘tall’ allele, SE = 0.003, P = 1 × 10−15, equivalent to 0.017 SD). There was little evidence of association between the allelic score and early infancy growth (0–3 months), but there was evidence of association between the allelic score and later growth. This association became stronger with each consecutive growth period, per ‘tall’ allele per month effects were 0.015 SD (3 months–1 year, SE = 0.004), 0.023 SD (1–3 years, SE = 0.003) and 0.028 SD (3–10 years, SE = 0.003). By age 10, the mean height difference between individuals with ≤170 versus ≥191 ‘tall’ alleles (the top and bottom 10%) was 4.7 cm (0.8 SD), explaining ∼5% of the variance. There was evidence of associations with specific growth periods for some SNPs (rs3791675, EFEMP1 and rs6569648, L3MBTL3) and supportive evidence for previously reported age-dependent effects of HHIP and SOCS2 SNPs. SNPs associated with adult height influence birth length and have an increasing effect on growth from late infancy through to late childhood. By age 10, they explain half the height variance (∼5%) of that explained in adults (∼10%).
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影响因子：
6.3
作者：
Howe, Laura D.;Tilling, Kate;Lawlor, Debbie A.
通讯作者：
Lawlor, Debbie A.
影响因子：
5.3
作者：
Macgregor, Stuart;Cornes, Belinda K.;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
影响因子：
2.5
作者：
Knight, B;Shields, BM;Hattersley, AT
通讯作者：
Hattersley, AT
影响因子：
30.8
作者：
Sanna, Serena;Jackson, Anne U.;Mohlke, Karen L.
通讯作者：
Mohlke, Karen L.
影响因子：
5.2
作者：
Howe, L. D.;Tilling, K.;Lawlor, D. A.
通讯作者：
Lawlor, D. A.