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儿童甲状腺功能的遗传决定因素
Tessa A Mulder1,2,3, Purdey J Campbell4, Peter N Taylor5
1Generation R Study Group, Erasmus University Medical Center, Rotterdam, CA 3000, The Netherlands.
European journal of endocrinology
|August 2, 2023
概括
影响甲状腺刺激激素 (TSH) 和自由甲状腺素 (FT4) 的遗传因素存在于儿童时期,有些影响比成人更大. 这项研究揭示了早期的甲状腺功能遗传调节.
科学领域:
- 内分泌学 在内分泌学.
- 遗传学 遗传学 是一个
- 儿科 儿科 儿科
背景情况:
- 全基因组关联研究已经确定了许多与成年人甲状腺刺激激素 (TSH) 和自由甲状腺素 (FT4) 度相关的遗传位置.
- 这些遗传决定因素对甲状腺功能的年龄相关影响尚未被彻底研究.
研究的目的:
- 调查TSH和FT4先前确定的遗传决定因子与新生儿和儿童中这些激素度的关联.
- 评估基因变异对甲状腺功能影响的潜在年龄相关变异.
主要方法:
- 利用了来自三个潜在的基于人口的队列的数据:R世代,父母和儿童的艾文纵向研究 (ALSPAC) 和布里斯班纵向双胞胎研究 (BLTS).
- 使用多变量线性回归分析了单核酸多态 (SNPs) 和TSH/FT4度之间的关联.
- 构建加权多基因风险评分 (PRS) 来聚合SNP影响.
主要成果:
- 在儿童时期,SNP的很大一部分 (TSH为30/60,FT为11/31) 经过多次测试校正后显示与甲状腺功能有关.
- 特定基因 (AADAT,GLIS3,TM4SF4,VEGFA) 的效应大小在儿童中明显大于成人.
- TSH和FT4 PRS解释了度变化的很大一部分 (TSH为5.3%-8.4%,FT为1.5%-4.2%).
- 五个TSH相关SNP在新生儿中显示出相关性,而在这个年龄组中没有发现FT4相关SNP.
结论:
- 许多已知影响甲状腺功能的遗传变异已经在儿童时期活跃.
- 某些遗传决定因素对甲状腺激素的影响在儿童中可能比成人更明显.
- 这些发现为早期发育过程中甲状腺功能的遗传调节提供了新的见解.
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