LIN28B 的不同变异体影响从出生到成年的身高增长。

Distinct variants at LIN28B influence growth in height from birth to adulthood.

机构信息

Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.

出版信息

Am J Hum Genet. 2010 May 14;86(5):773-82. doi: 10.1016/j.ajhg.2010.03.010. Epub 2010 Apr 15.

Abstract

We have studied the largely unknown genetic underpinnings of height growth by using a unique resource of longitudinal childhood height data available in Finnish population cohorts. After applying GWAS mapping of potential genes influencing pubertal height growth followed by further characterization of the genetic effects on complete postnatal growth trajectories, we have identified strong association between variants near LIN28B and pubertal growth (rs7759938; female p = 4.0 x 10(-9), male p = 1.5 x 10(-4), combined p = 5.0 x 10(-11), n = 5038). Analysis of growth during early puberty confirmed an effect on the timing of the growth spurt. Correlated SNPs have previously been implicated as influencing both adult stature and age at menarche, the same alleles associating with taller height and later age of menarche in other studies as with later pubertal growth here. Additionally, a partially correlated LIN28B SNP, rs314277, has been associated previously with final height. Testing both rs7759938 and rs314277 (pairwise r(2) = 0.29) for independent effects on postnatal growth in 8903 subjects indicated that the pubertal timing-associated marker rs7759938 affects prepubertal growth in females (p = 7 x 10(-5)) and final height in males (p = 5 x 10(-4)), whereas rs314277 has sex-specific effects on growth (p for interaction = 0.005) that were distinct from those observed at rs7759938. In conclusion, partially correlated variants at LIN28B tag distinctive, complex, and sex-specific height-growth-regulating effects, influencing the entire period of postnatal growth. These findings imply a critical role for LIN28B in the regulation of human growth.

摘要

我们利用芬兰人群队列中可用的独特纵向儿童身高数据资源,研究了身高增长的主要未知遗传基础。在应用潜在基因影响青春期身高增长的 GWAS 图谱绘制后,我们进一步描述了对完全出生后生长轨迹的遗传影响,我们已经确定了 LIN28B 附近变体与青春期生长之间的强烈关联(rs7759938;女性 p = 4.0 x 10(-9),男性 p = 1.5 x 10(-4),合并 p = 5.0 x 10(-11),n = 5038)。对早期青春期生长的分析证实了对生长突增时间的影响。以前,相关的 SNP 被认为会影响成年身高和初潮年龄,在其他研究中,相同的等位基因与更高的身高和初潮年龄较晚相关,与这里青春期生长较晚相关。此外,先前与最终身高相关的部分相关 LIN28B SNP rs314277 也与最终身高相关。在 8903 名受试者中测试 rs7759938 和 rs314277(成对 r(2) = 0.29)对出生后生长的独立影响表明,与青春期相关的标记物 rs7759938 会影响女性的青春期前生长(p = 7 x 10(-5)) 和男性的最终身高(p = 5 x 10(-4)),而 rs314277 对生长具有性别特异性影响(p 为交互作用 = 0.005),与在 rs7759938 中观察到的不同。总之,LIN28B 上部分相关的变体可标记出独特、复杂且具有性别特异性的身高生长调节作用,影响整个出生后生长阶段。这些发现意味着 LIN28B 在人类生长调节中起着关键作用。

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