对遗传变异和基因表达的整体分析确定了心血管疾病表型的网络
Chen Yao1, Brian H Chen1, Roby Joehanes1
1From the National Heart, Lung, and Blood Institute's Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., L.A.C., C.S.F., P.C., C.J.O'D., D.L.); Population Sciences Branch, National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (C.Y., B.H.C., R.J., X.Z., C.L., T.H., P.C., D.L.); Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD (R.J., P.J.M.); Department of Computer Engineering, Middle East Technical University, Ankara, Turkey (B.O.); Department of Computer Engineering, Bilkent University, Ankara, Turkey (O.T.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (L.A.C.); Harvard Medical School, Boston, MA (J.B.M.); Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (C.S.F.); Department of Medicine, University of Massachusetts Medical School, Worchester (J.E.F.); Division of Cardiology, Massachusetts General Hospital, Boston, MA (C.J.O'D.); and Departments of Statistics and of Biostatistics and Medical Informatics, University of Wisconsin-Madison (S.K.).
研究人员创建了一个心血管疾病 (CVD) 网络,将遗传变异 (SNP) 与特征联系起来. 这个网络确定了影响心血管疾病风险因素的基因表达变化,提供了潜在的药物标.
科学领域:
- 遗传学 是一个遗传学.
- 心血管医学 心血管医学
- 系统生物学 系统生物学
背景情况:
- 心血管疾病 (CVD) 涉及复杂的特征,许多相关的单核酸多态 (SNP) 已被确定,但它们的功能作用尚不清楚.
- 全基因组关联研究 (GWAS) 已经将许多SNP与心血管疾病联系起来,但了解它们对疾病机制的贡献仍然是一个挑战.
研究的目的:
- 构建一个综合性网络,整合具有多种心血管疾病特征的遗传变异 (SNP).
- 探索SNP与基因表达之间的关系,以及它们与心血管疾病风险因素的关联.
- 通过分析SNP基因表达网络来确定心血管疾病的潜在治疗点.
主要方法:
- 使用来自GWAS的21个CVD特征相关的1512个SNP构建了一个CVD网络.
- 从5257名弗雷明汉心脏研究参与者的全血基因表达数据中分析了与这些SNP相关的数据.
- 确定表达量的特征位点 (eQTL),并检查它们与心血管疾病风险因素 (脂质,血压,BMI,葡萄糖) 的关联.
主要成果:
- 建立了一个由1512个SNP和21个CVD特征组成的网络,揭示了跨特征的连接.
- 确定了370个cis-eQTL和44个trans-eQTL,形成了13个CVD相关模块.
- eQTL基因表达与心血管疾病风险因素显著相关,调解分析表明SNP通过eQTL基因表达影响表型.
结论:
- 一种网络方法成功地集成了SNP-表型和SNP-转录数据用于CVD.
- 已确定的生物通路和基因表达网络为预防和治疗心血管疾病提供了对潜在药物点的见解.
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