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大脑、脑脊液和血浆蛋白质组的基因组图谱优先考虑与神经紊乱相关的蛋白质。

Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders.

机构信息

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.

NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.

出版信息

Nat Neurosci. 2021 Sep;24(9):1302-1312. doi: 10.1038/s41593-021-00886-6. Epub 2021 Jul 8.

DOI:10.1038/s41593-021-00886-6
PMID:34239129
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8521603/
Abstract

Understanding the tissue-specific genetic controls of protein levels is essential to uncover mechanisms of post-transcriptional gene regulation. In this study, we generated a genomic atlas of protein levels in three tissues relevant to neurological disorders (brain, cerebrospinal fluid and plasma) by profiling thousands of proteins from participants with and without Alzheimer's disease. We identified 274, 127 and 32 protein quantitative trait loci (pQTLs) for cerebrospinal fluid, plasma and brain, respectively. cis-pQTLs were more likely to be tissue shared, but trans-pQTLs tended to be tissue specific. Between 48.0% and 76.6% of pQTLs did not co-localize with expression, splicing, DNA methylation or histone acetylation QTLs. Using Mendelian randomization, we nominated proteins implicated in neurological diseases, including Alzheimer's disease, Parkinson's disease and stroke. This first multi-tissue study will be instrumental to map signals from genome-wide association studies onto functional genes, to discover pathways and to identify drug targets for neurological diseases.

摘要

了解蛋白质水平的组织特异性遗传控制对于揭示转录后基因调控的机制至关重要。在这项研究中，我们通过对来自患有和不患有阿尔茨海默病的参与者的数千种蛋白质进行分析，生成了与神经紊乱相关的三种组织（大脑、脑脊液和血浆）中蛋白质水平的基因组图谱。我们分别鉴定出了 274、127 和 32 个脑脊液、血浆和大脑的蛋白质数量性状基因座（pQTLs）。顺式 pQTL 更有可能是组织共享的，但反式 pQTL 则倾向于组织特异性。在 pQTL 中，有 48.0%到 76.6%的与表达、剪接、DNA 甲基化或组蛋白乙酰化 QTL 没有共定位。通过孟德尔随机化，我们提名了一些与神经疾病相关的蛋白质，包括阿尔茨海默病、帕金森病和中风。这项多组织的首次研究将有助于将全基因组关联研究的信号映射到功能基因上，以发现通路并确定神经疾病的药物靶点。

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2
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3
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4
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5
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