PT - JOURNAL ARTICLE AU - Yao, Chen AU - Chen, George AU - Song, Ci AU - Mendelson, Michael AU - Huan, Tianxiao AU - Laser, Annika AU - Wu, Hongsheng AU - Ho, Jennifer E. AU - Courchesne, Paul AU - Lyass, Asya AU - Larson, Martin G. AU - Gieger, Christian AU - Graumann, Johannes AU - Johnson, Andrew D. AU - Hwang, Shih-Jen AU - Liu, Chunyu AU - Suhre, Karsten AU - Levy, Daniel TI - Genome-wide Association Study Of Plasma Proteins Identifies Putatively Causal Genes, Proteins, And Pathways For Cardiovascular Disease AID - 10.1101/136523 DP - 2017 Jan 01 TA - bioRxiv PG - 136523 4099 - http://biorxiv.org/content/early/2017/05/12/136523.short 4100 - http://biorxiv.org/content/early/2017/05/12/136523.full AB - Identifying genetic variants associated with circulating protein concentrations (pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome’s causal role in disease and bridge a GWAS knowledge gap for hitherto unexplained SNP-disease associations. We conducted GWAS of 71 high-value proteins for cardiovascular disease in 6,861 Framingham Heart Study participants followed by external replication. We comprehensively mapped thousands of pQTLs, including functional annotations and clinical-trait associations, and created an integrated plasma-protein-QTL searchable database. We next identified 15 proteins with pQTLs coinciding with coronary heart disease (CHD)-related variants from GWAS or tested causal for CHD by Mendelian randomization; most of these proteins were associated with new-onset cardiovascular disease events in Framingham participants with long-term follow-up. Identifying pQTLs and integrating them with GWAS results yields insights into genes, proteins, and pathways that may be causally associated with disease and can serve as therapeutic targets for treatment and prevention.