Connecting genetic risk to disease endpoints through the human blood plasma proteome
Genome-wide association studies (GWAS) with intermediate phenotypes, like changes in metabolite and protein levels, provide functional evidence for mapping disease associations and translating them into clinical applications. However, although hundreds of genetic risk variants have been associated with complex disorders, the underlying molecular pathways often remain elusive. Associations with intermediate traits across multiple chromosome locations are key in establishing functional links between GWAS-identified risk-variants and disease endpoints. Here, we describe a GWAS performed with a highly multiplexed aptamer-based affinity proteomics platform. We quantified associations between protein level changes and gene variants in a German cohort and replicated this GWAS in an Arab/Asian cohort. We identified many independent, SNP-protein associations, which represent novel, inter-chromosomal links, related to autoimmune disorders, Alzheimer’s disease, cardiovascular disease, cancer, and many other disease endpoints. We integrated this information into a genome-proteome network, and created an interactive web-tool for interrogations. Our results provide a basis for new approaches to pharmaceutical and diagnostic applications.
Date: 1 December 2016, 14:00
Venue: Wellcome Trust Centre for Human Genetics, Headington OX3 7BN
Venue Details: Rooms A&B
Speaker: Prof. Dr. Karsten Suhre (Weill Cornell Medical College, Qatar )
Organising department: Wellcome Trust Centre for Human Genetics
Organisers: Christine Webb (University of Oxford, Wellcome Trust Centre for Human Genetics), Susan Wilson (University of Oxford, Wellcome Trust Centre for Human Genetics), Professor Catherine Green (University of Oxford)
Host: Prof Mark McCarthy (University of Oxford)
Part of: WHG Seminars
Topics:
Booking required?: Not required
Audience: Members of the University only
Editor: Isabel Schmidt