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 w...
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Published in | bioRxiv |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , |
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Cold Spring Harbor
Cold Spring Harbor Laboratory Press
09.11.2016
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Abstract | 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. |
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AbstractList | 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. |
Author | Bhagwat, Aditya Al-Dous, Eman K Grallert, Harald Arnold, Matthias Peters, Annette Thareja, Gaurav Robert Kirk Delisle Raffler, Johannes Pezer, Marija Engelke, Rudolf Laser, Annika Sarwath, Hina Gold, Larry Mook-Kanamori, Dennis O Cotton, Richard J Malek, Joel El-Din Selim, Mohammed A Mohamoud, Yasmin A Suhre, Karsten Strauch, Konstantin Graumann, Johannes Gieger, Christian Lauc, Gordan Kastenmuller, Gabi |
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SubjectTerms | Alzheimer's disease Aptamers Autoimmune diseases Cardiovascular diseases Gene mapping Genome-wide association studies Genomes Health risk assessment Neurodegenerative diseases Peptide mapping Phenotypes Proteins Proteomics Single-nucleotide polymorphism Therapeutic applications |
Title | Connecting genetic risk to disease endpoints through the human blood plasma proteome |
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