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 - 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 -