Genomic atlas of the human plasma proteome.
Genomic atlas of the human plasma proteome.
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DOI：
10.1038/s41586-018-0175-2
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发表时间：
2018-06
期刊：
影响因子：
64.8
通讯作者：
Butterworth AS
中科院分区：
文献类型：
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作者：
Sun BB;Maranville JC;Peters JE;Stacey D;Staley JR;Blackshaw J;Burgess S;Jiang T;Paige E;Surendran P;Oliver-Williams C;Kamat MA;Prins BP;Wilcox SK;Zimmerman ES;Chi A;Bansal N;Spain SL;Wood AM;Morrell NW;Bradley JR;Janjic N;Roberts DJ;Ouwehand WH;Todd JA;Soranzo N;Suhre K;Paul DS;Fox CS;Plenge RM;Danesh J;Runz H;Butterworth AS
虽然血浆蛋白在生物学过程中具有重要作用，并且是许多药物的直接靶点，但控制血浆蛋白水平个体间差异的遗传因素尚未得到很好的理解。在这里，我们描述了INTERVAL研究中健康献血者血浆蛋白质组的遗传结构。我们确定了1，478种蛋白质的1，927种遗传关联，是现有知识的四倍，包括1，104种蛋白质的反式关联。为了了解血浆蛋白水平扰动的后果，我们采用了一种综合方法，将遗传变异与生物学途径、疾病和药物数据库联系起来。我们发现，蛋白质数量性状基因座与基因表达数量性状基因座重叠，以及与疾病相关的基因座，并发现证据表明，蛋白质生物标志物在疾病中具有因果作用，使用孟德尔随机化分析。通过将遗传因素与疾病通过特定的蛋白质联系起来，我们的分析突出了潜在的治疗靶点，将现有药物与新疾病适应症相匹配的机会，以及正在开发的药物的潜在安全性问题。
Although plasma proteins have important roles in biological processes and are the direct targets of many drugs, the genetic factors that control inter-individual variation in plasma protein levels are not well understood. Here we characterize the genetic architecture of the human plasma proteome in healthy blood donors from the INTERVAL study. We identify 1,927 genetic associations with 1,478 proteins, a fourfold increase on existing knowledge, including trans associations for 1,104 proteins. To understand the consequences of perturbations in plasma protein levels, we apply an integrated approach that links genetic variation with biological pathway, disease, and drug databases. We show that protein quantitative trait loci overlap with gene expression quantitative trait loci, as well as with disease-associated loci, and find evidence that protein biomarkers have causal roles in disease using Mendelian randomization analysis. By linking genetic factors to diseases via specific proteins, our analyses highlight potential therapeutic targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development.
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DOI：
10.1016/s0140-6736(17)31928-1
发表时间：
2017-11-25
期刊：
Lancet (London, England)
影响因子：
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作者：
Di Angelantonio E;Thompson SG;Kaptoge S;Moore C;Walker M;Armitage J;Ouwehand WH;Roberts DJ;Danesh J;INTERVAL Trial Group
通讯作者：
INTERVAL Trial Group
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
DOI：
10.1126/science.1260793
发表时间：
2015-02-06
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Battle A;Khan Z;Wang SH;Mitrano A;Ford MJ;Pritchard JK;Gilad Y
通讯作者：
Gilad Y
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
全基因组关联研究将CSF1，OPTN和TNFRSF11A的变体确定为Paget骨骼疾病的遗传危险因素。
影响因子：
30.8
作者：
通讯作者：
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