出生体重的全基因组关联与成人疾病的相关性
Momoko Horikoshi1,2, Robin N Beaumont3, Felix R Day4
1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Nature
|September 30, 2016
概括
出生体重与成人疾病有关. 遗传因素,不仅仅是早期的环境,显著影响了生理学和未来的心脏代谢健康,揭示了共同的遗传途径.
科学领域:
- 遗传学
- 代谢疾病
- 发育生物学
背景情况:
- 出生体重与2型糖尿病和心血管疾病等成年代谢疾病有关.
- 这些关联往往归因于早期的环境因素.
- 胎儿和母亲的因素影响BW.
研究的目的:
- 使用多祖先全基因组关联研究 (GWAS) 调查BW的遗传基础.
- 确定胎儿遗传变异对BW的影响程度.
- 探索BW与成人心脏代谢风险因素之间的遗传相关性.
主要方法:
- 在超过153,000个个体中进行了多祖先GWAS元分析.
- 评估由胎儿遗传变异解释的BW变异的百分比.
- 计算了BW和心脏代谢特征之间的遗传相关性 (静脉血压,T2D,冠状动脉疾病).
主要成果:
- 确定了与BW相关的60个位点,胎儿基因型解释了BW差异的约15%.
- 发现BW与静脉压,T2D和冠状动脉疾病之间存在显著的逆遗传相关性.
- 证明遗传因素是BW和未来心脏代谢风险之间负面共变的一个主要因素.
- 路径分析显示胰岛素信号,葡萄糖平衡和染色质重塑的丰富性.
结论:
- 共同的遗传效应有助于早期生长 (BW) 和成人心脏代谢疾病之间的联系.
- 确定了这些共同遗传效应的特定生物途径.
- 突显胎儿遗传在长期健康状况中的作用.
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