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

By Karsten Suhre, M. Arnold, A. Bhagwat, Richard J. Cotton, R. Engelke, Johannes Raffler, H. Sarwath, G. Thareja, Annika Wahl, R. K. DeLisle and 14 more. Nature Communications, 2016

740 citations recorded by the source corpus.

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. Individual genetic variation can affect the levels of protein in blood, but detailed data sets linking these two types of data are rare. Here, the authors carry out a genome-wide association study of levels of over a thousand different proteins, and describe many new SNP-protein interactions.

Subfields: Genetics, Molecular Biology, Spectroscopy

View Paper: https://www.semanticscholar.org/paper/7f3552649ca373931e86e7e99d382ae50f2f0c03

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In Genetics

  1. George Davey Smith
  2. Stephen Burgess
  3. Gibran Hemani
  4. J. Bowden
  5. Michael Holmes
  6. S. Thompson
  7. Philip C. Haycock
  8. Adam S. Butterworth

In Molecular Biology

  1. George Davey Smith
  2. Gibran Hemani
  3. John A. Todd
  4. Robert M. Plenge
  5. Karsten Suhre
  6. Tom R. Gaunt
  7. Willem H. Ouwehand

In Spectroscopy

  1. Karsten Suhre

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