心脏代谢风险位点下游共享跨组织和疾病的 cis 和 trans 基因调节
Oscar Franzén1, Raili Ermel2, Ariella Cohain3
1Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York , NY 10029, USA. Clinical Gene Networks AB, Jungfrugatan 10, 114 44 Stockholm, Sweden.
Science (New York, N.Y.)
|August 20, 2016
概括
全基因组关联研究 (GWAS) 揭示了心脏代谢疾病 (CMD) 风险位置,但机制尚不清楚. STARNET研究发现共享和组织特异性基因调节,突出腹部脂肪
科学领域:
- 遗传学
- 心血管生物学
- 代谢学
背景情况:
- 全基因组关联研究 (GWAS) 已经确定了与心脏代谢疾病 (CMD) 风险相关的众多遗传位置.
- 然而,这些位点解释了一小部分的遗传变异,它们的下游基因调节机制在很大程度上是未知的.
- 了解这些机制对于将遗传发现转化为临床应用至关重要.
研究的目的:
- 通过GWAS确定基因调节机制的心脏代谢疾病 (CMD) 风险位.
- 探索不同血管和代谢组织的共同和组织特异性调节效应.
- 确定参与CMD病变的关键组织和基因.
主要方法:
- 来自600名冠状动脉疾病患者的血管和代谢组织的基因型和RNA测序 (斯德哥尔摩-塔尔图动脉样逆转网络工程任务研究 - STARNET).
- 与CMD风险单核酸多态 (SNP) 相关的基因表达特征的分析.
- 对不同组织的调节效应进行比较,并与现有的基因-组织表达研究进行比较.
主要成果:
- 在STARNET中经常观察到与GWAS识别的CMD风险SNP相关的基因表达特征,这表明整个组织和疾病的共享cis/ trans基因调节.
- 相反,一些GWAS风险SNP调节作用是组织特异性的,腹部脂肪是血液脂质的重要调节部位.
- 低密度脂蛋白胆固醇和冠状动脉疾病风险基因PCSK9被确定为腹部脂肪组织特异性调节的一个例子.
结论:
- STARNET研究提供了有关心脏代谢疾病 (CMD) 风险位的基因调节机制的宝贵见解.
- 结果表明共享的调节途径和组织特异性影响,强调特定组织的作用,如腹部脂肪.
- 这项研究有助于将遗传发现转化为潜在的CMD诊断,治疗和预防策略.
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