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

Karsten Suhre (), Matthias Arnold, Aditya Mukund Bhagwat, Richard J. Cotton, Rudolf Engelke, Johannes Raffler, Hina Sarwath, Gaurav Thareja, Annika Wahl, Robert Kirk DeLisle, Larry Gold, Marija Pezer, Gordan Lauc, Mohammed A. El-Din Selim, Dennis O. Mook-Kanamori, Eman K. Al-Dous, Yasmin A. Mohamoud, Joel Malek, Konstantin Strauch, Harald Grallert, Annette Peters, Gabi Kastenmüller, Christian Gieger () and Johannes Graumann ()
Additional contact information
Karsten Suhre: Weill Cornell Medicine-Qatar, Education City
Matthias Arnold: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health
Aditya Mukund Bhagwat: Proteomics Core, Weill Cornell Medicine-Qatar, Education City
Richard J. Cotton: Proteomics Core, Weill Cornell Medicine-Qatar, Education City
Rudolf Engelke: Proteomics Core, Weill Cornell Medicine-Qatar, Education City
Johannes Raffler: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health
Hina Sarwath: Proteomics Core, Weill Cornell Medicine-Qatar, Education City
Gaurav Thareja: Weill Cornell Medicine-Qatar, Education City
Annika Wahl: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Robert Kirk DeLisle: SomaLogic
Larry Gold: SomaLogic
Marija Pezer: Genos Ltd, Glycoscience Research Laboratory
Gordan Lauc: Genos Ltd, Glycoscience Research Laboratory
Mohammed A. El-Din Selim: Hamad Medical Corporation
Dennis O. Mook-Kanamori: Leiden University Medical Centre
Eman K. Al-Dous: Genomics Core, Weill Cornell Medicine-Qatar, Education City
Yasmin A. Mohamoud: Genomics Core, Weill Cornell Medicine-Qatar, Education City
Joel Malek: Genomics Core, Weill Cornell Medicine-Qatar, Education City
Konstantin Strauch: Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Harald Grallert: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Annette Peters: Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health
Gabi Kastenmüller: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health
Christian Gieger: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
Johannes Graumann: Proteomics Core, Weill Cornell Medicine-Qatar, Education City

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms14357

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