TY - JOUR
T1 - Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies
AU - CKDGen consortium
AU - Zhang, Jingning
AU - Dutta, Diptavo
AU - Köttgen, Anna
AU - Tin, Adrienne
AU - Schlosser, Pascal
AU - Grams, Morgan E.
AU - Harvey, Benjamin
AU - Yu, Bing
AU - Boerwinkle, Eric
AU - Coresh, Josef
AU - Chatterjee, Nilanjan
N1 - Funding Information:
The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). The authors thank the staff and participants of the ARIC study for their important contributions. SomaLogic Inc. conducted the SomaScan assays in exchange for use of ARIC data. This work was supported in part by NIH/NHLBI grant R01 HL134320. The UK Biobank data was obtained under the UK Biobank resource application 17712. Research of J.Z., D.D. and N.C. was supported by grant R01 from the National Human Genome Research Institute [1 R01 HG010480-01]. B.H. was supported by the Bloomberg Distinguished Professorship Endowment fund available to N.C. The work of A.K. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 431984000—SFB 1453. The work of P.S. was funded by the EQUIP Program for Medical Scientists, Faculty of Medicine, University of Freiburg. The work of A.T. was funded by R01 AR073178. The work of J.C. and E.B. was funded by the ARIC contract. The work of M.G. and J.C. was funded by the multiomics grant R01 DK124399. The work of B.Y. was funded by HL148218. We acknowledge N. Mancuso and A. Gusev for providing preliminary TWAS models built with GTEx V8 data.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/5
Y1 - 2022/5
N2 - Improved understanding of genetic regulation of the proteome can facilitate identification of the 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 Atherosclerosis Risk in Communities study, and further replicated findings on 467 AA individuals from the African American Study of Kidney Disease and Hypertension study. Here, we identified 2,004 proteins in EA and 1,618 in AA, with most overlapping, which showed associations with common variants in cis-regions. Availability of AA samples led to smaller credible sets and notable number of population-specific cis-protein quantitative trait loci. Elastic Net produced powerful models for protein prediction in both populations. An application of proteome-wide association studies 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 to investigate the genetic mechanisms of molecular phenotypes and their relationship with complex traits.
AB - Improved understanding of genetic regulation of the proteome can facilitate identification of the 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 Atherosclerosis Risk in Communities study, and further replicated findings on 467 AA individuals from the African American Study of Kidney Disease and Hypertension study. Here, we identified 2,004 proteins in EA and 1,618 in AA, with most overlapping, which showed associations with common variants in cis-regions. Availability of AA samples led to smaller credible sets and notable number of population-specific cis-protein quantitative trait loci. Elastic Net produced powerful models for protein prediction in both populations. An application of proteome-wide association studies 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 to investigate the genetic mechanisms of molecular phenotypes and their relationship with complex traits.
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U2 - 10.1038/s41588-022-01051-w
DO - 10.1038/s41588-022-01051-w
M3 - Article
C2 - 35501419
AN - SCOPUS:85130344623
SN - 1061-4036
VL - 54
SP - 593
EP - 602
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -