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

Karsten Suhre, Matthias Arnold, Aditya 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 Aldous, Yasmin Ali Mohamoud, Joel Malek, Konstantin Strauch, Harald Grallert & 4 others Annette Peters, Gabi Kastenmüller, Christian Gieger, Johannes Graumann

Research output: Contribution to journalArticle

49 Citations (Scopus)

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.

Original languageEnglish
Article number14357
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 27 Feb 2017

Fingerprint

proteome
blood plasma
genome
Genome-Wide Association Study
Proteome
Blood
Genes
Plasmas
Genetic Loci
proteins
Proteomics
phenotype
metabolites
interrogation
Proteins
loci
Genome
genes
Phenotype
affinity

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Connecting genetic risk to disease end points through the human blood plasma proteome. / Suhre, Karsten; Arnold, Matthias; Bhagwat, Aditya; Cotton, Richard J.; Engelke, Rudolf; Raffler, Johannes; Sarwath, Hina; Thareja, Gaurav; Wahl, Annika; Delisle, Robert Kirk; Gold, Larry; Pezer, Marija; Lauc, Gordan; Selim, Mohammed A El Din; Mook-Kanamori, Dennis O.; Aldous, Eman; Ali Mohamoud, Yasmin; Malek, Joel; Strauch, Konstantin; Grallert, Harald; Peters, Annette; Kastenmüller, Gabi; Gieger, Christian; Graumann, Johannes.

In: Nature Communications, Vol. 8, 14357, 27.02.2017.

Research output: Contribution to journalArticle

Suhre, K, Arnold, M, Bhagwat, A, Cotton, RJ, Engelke, R, Raffler, J, Sarwath, H, Thareja, G, Wahl, A, Delisle, RK, Gold, L, Pezer, M, Lauc, G, Selim, MAED, Mook-Kanamori, DO, Aldous, E, Ali Mohamoud, Y, Malek, J, Strauch, K, Grallert, H, Peters, A, Kastenmüller, G, Gieger, C & Graumann, J 2017, 'Connecting genetic risk to disease end points through the human blood plasma proteome', Nature Communications, vol. 8, 14357. https://doi.org/10.1038/ncomms14357
Suhre, Karsten ; Arnold, Matthias ; Bhagwat, Aditya ; Cotton, Richard J. ; Engelke, Rudolf ; Raffler, Johannes ; Sarwath, Hina ; Thareja, Gaurav ; Wahl, Annika ; Delisle, Robert Kirk ; Gold, Larry ; Pezer, Marija ; Lauc, Gordan ; Selim, Mohammed A El Din ; Mook-Kanamori, Dennis O. ; Aldous, Eman ; Ali Mohamoud, Yasmin ; Malek, Joel ; Strauch, Konstantin ; Grallert, Harald ; Peters, Annette ; Kastenmüller, Gabi ; Gieger, Christian ; Graumann, Johannes. / Connecting genetic risk to disease end points through the human blood plasma proteome. In: Nature Communications. 2017 ; Vol. 8.
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