TY - JOUR T1 - Connecting genetic risk to disease endpoints through the human blood plasma proteome JF - bioRxiv DO - 10.1101/086793 SP - 086793 AU - Karsten Suhre AU - Matthias Arnold AU - Aditya Bhagwat AU - Richard J. Cotton AU - Rudolf Engelke AU - Annika Laser AU - Johannes Raffler AU - Hina Sarwath AU - Gaurav Thareja AU - Robert Kirk DeLisle AU - Larry Gold AU - Marija Pezer AU - Gordan Lauc AU - Mohammed A. El-Din Selim AU - Dennis O. Mook-Kanamori AU - Eman K. Al-Dous AU - Yasmin A. Mohamoud AU - Joel Malek AU - Konstantin Strauch AU - Harald Grallert AU - Annette Peters AU - Gabi Kastenmuller AU - Christian Gieger AU - Johannes Graumann Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/11/09/086793.abstract N2 - 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. ER -