Connecting genetic risk to disease endpoints through the human blood plasma proteome
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.
Cotton Richard J.、Suhre Karsten、Arnold Matthias、Bhagwat Aditya、DeLisle Robert Kirk、Pezer Marija、Lauc Gordan、Mook-Kanamori Dennis O.、Al-Dous Eman K.、Malek Joel、Kastenmuller Gabi、Thareja Gaurav、Laser Annika、Raffler Johannes、Strauch Konstantin、Gieger Christian、Sarwath Hina、Gold Larry、Peters Annette、Selim Mohammed A. El-Din、Graumann Johannes、Engelke Rudolf、Mohamoud Yasmin A.、Grallert Harald
Proteomics CoreDepartment of Physiology and BiophysicsInstitute of Bioinformatics and Systems BiologyProteomics CoreSomaLogicGenos LtdGenos LtdLeiden University Medical CentreGenomics CoreGenomics CoreInstitute of Bioinformatics and Systems Biology||German Center for Diabetes Research (DZD)Department of Physiology and BiophysicsResearch Unit of Molecular EpidemiologyInstitute of Bioinformatics and Systems BiologyInstitute of Genetic Epidemiology||Institute of Medical InformaticsResearch Unit of Molecular Epidemiology||Institute of Epidemiology II||German Center for Diabetes Research (DZD)Proteomics CoreSomaLogicInstitute of Epidemiology II||German Center for Diabetes Research (DZD)||German Center for Cardiovascular Disease Research (DZHK)Department of DermatologyProteomics CoreProteomics CoreGenomics CoreResearch Unit of Molecular Epidemiology||Institute of Epidemiology II||German Center for Diabetes Research (DZD)
医学研究方法基础医学生物科学研究方法、生物科学研究技术
Cotton Richard J.,Suhre Karsten,Arnold Matthias,Bhagwat Aditya,DeLisle Robert Kirk,Pezer Marija,Lauc Gordan,Mook-Kanamori Dennis O.,Al-Dous Eman K.,Malek Joel,Kastenmuller Gabi,Thareja Gaurav,Laser Annika,Raffler Johannes,Strauch Konstantin,Gieger Christian,Sarwath Hina,Gold Larry,Peters Annette,Selim Mohammed A. El-Din,Graumann Johannes,Engelke Rudolf,Mohamoud Yasmin A.,Grallert Harald.Connecting genetic risk to disease endpoints through the human blood plasma proteome[EB/OL].(2025-03-28)[2025-07-16].https://www.biorxiv.org/content/10.1101/086793.点此复制
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