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Suhre, K.* ; Arnold, M. ; Bhagwat, A.M.* ; Cotton, R.J.* ; Engelke, R.* ; Raffler, J. ; Sarwath, H.* ; Thareja, G.* ; Wahl, A. ; DeLisle, R.K.* ; Gold, L.* ; Pezer, M.* ; Lauc, G.* ; El-Din Selim, M.A.* ; Mook-Kanamori, D.O.* ; Al-Dous, E.K.* ; Mohamoud, Y.A.* ; Malek, J.A.* ; Strauch, K. ; Grallert, H. ; Peters, A. ; Kastenmüller, G. ; Gieger, C. ; Graumann, J.*

Connecting genetic risk to disease end points through the human blood plasma proteome.

Nat. Commun. 8:14357 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Genome-wide association studies (GWAS) with intermediate phenotypes, like changes in metabolite and protein levels, provide functional evidence to map disease associations and translate them into clinical applications. However, although hundreds of genetic variants have been associated with complex disorders, the underlying molecular pathways often remain elusive. Associations with intermediate traits are key in establishing functional links between GWAS-identified risk-variants and disease end points. Here we describe a GWAS using a highly multiplexed aptamer-based affinity proteomics platform. We quantify 539 associations between protein levels and gene variants (pQTLs) in a German cohort and replicate over half of them in an Arab and Asian cohort. Fifty-five of the replicated pQTLs are located in trans. Our associations overlap with 57 genetic risk loci for 42 unique disease end points. We integrate this information into a genome-proteome network and provide an interactive web-tool for interrogations. Our results provide a basis for novel approaches to pharmaceutical and diagnostic applications.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide; Alzheimers-disease; Rheumatoid-arthritis; Transcription Factor; Endothelial-cells; Human Metabolism; E-selectin; Identification; Variants; Association
Language english
Publication Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 8, Issue: , Pages: , Article Number: 14357 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
Institute of Bioinformatics and Systems Biology (IBIS)
POF-Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
90000 - German Center for Diabetes Research
30505 - New Technologies for Biomedical Discoveries
Research field(s) Genetics and Epidemiology
Enabling and Novel Technologies
PSP Element(s) G-504091-004
G-504100-001
G-504000-005
G-501900-402
G-503700-001
PubMed ID 28240269
DOI 10.1038/ncomms14357
WOS ID WOS:000394795300001
Scopus ID 85014061753
Erfassungsdatum 2017-03-17
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