Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies.
Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies.
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DOI：
10.1038/s41588-022-01051-w
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发表时间：
2022-05
期刊：
影响因子：
30.8
通讯作者：
Chatterjee, Nilanjan
中科院分区：
文献类型：
--
作者：
Zhang, Jingning;Dutta, Diptavo;Koettgen, Anna;Tin, Adrienne;Schlosser, Pascal;Grams, Morgan E.;Harvey, Benjamin;Yu, Bing;Boerwinkle, Eric;Coresh, Josef;Chatterjee, Nilanjan
提高对蛋白质组遗传调控的理解可以促进复杂性状因果机制的识别。我们分析了 ARIC 研究中 7,213 名欧洲裔美国人 (EA) 和 1,871 名非洲裔美国人 (AA) 个体的 4,657 种血浆蛋白数据，并进一步重复了 AASK 研究中 467 名 AA 个体的研究结果。在这里，我们鉴定了 EA 中的 2,004 个蛋白质和 AA 中的 1,618 个蛋白质，其中大部分重叠，这表明与顺式区域中的常见变异相关。 AA 样本的可用性导致了较小的可信集和大量的群体特异性顺式 pQTL。 Elastic-net 为这两个群体的蛋白质预测提供了强大的模型。全蛋白质组关联研究 (PWAS) 在血清尿酸盐和痛风中的应用，涉及包括 IL1RN 在内的多种蛋白质，揭示了阿那白滞素药物治疗急性痛风发作的前景。我们的研究证明了大规模和多样化的祖先研究对于分子表型遗传机制及其与复杂性状的关系的价值。
Improved understanding of genetic regulation of proteome can facilitate the identification of causal mechanisms for complex traits. We analyzed data on 4,657 plasma proteins from 7,213 European American (EA) and 1,871 African American (AA) individuals from the ARIC study, and further replicated findings on 467 AA individuals from the AASK study. Here we identified 2,004 proteins in EA and 1,618 in AA, with majority overlapping, which showed associations with common variants in cis-regions. Availability of AA samples led to smaller credible sets and significant number of population-specific cis-pQTLs. Elastic-net produced powerful models for protein prediction in both populations. An application of proteome-wide association studies (PWAS) to serum urate and gout, implicated several proteins, including IL1RN, revealing the promise of the drug anakinra to treat acute gout flares. Our study demonstrates the value of large and diverse ancestry study for genetic mechanisms of molecular phenotypes and their relationship with complex traits.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
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
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
影响因子：
17.1
作者：
Finan C;Gaulton A;Kruger FA;Lumbers RT;Shah T;Engmann J;Galver L;Kelley R;Karlsson A;Santos R;Overington JP;Hingorani AD;Casas JP
通讯作者：
Casas JP
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen