Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease

Chen Yao, George Chen, Ci Song, Joshua Keefe, Michael Mendelson, Tianxiao Huan, Benjamin B. Sun, Annika Laser, Joseph C. Maranville, Hongsheng Wu, Jennifer E. Ho, Paul Courchesne, Asya Lyass, Martin G. Larson, Christian Gieger, Johannes Graumann, Andrew D. Johnson, John Danesh, Heiko Runz, Shih Jen Hwang & 4 others Chunyu Liu, Adam S. Butterworth, Karsten Suhre, Daniel Levy

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome’s causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in 6861 Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment.

Original languageEnglish
Article number3268
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Fingerprint

genes
Blood Proteins
Cardiovascular Diseases
Genes
proteins
Genome-Wide Association Study
genome
Proteins
Random Allocation
Coronary Disease
proteome
Protein Databases
Proteome
Ports and harbors
harbors
loci
Single Nucleotide Polymorphism
Testing

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease. / Yao, Chen; Chen, George; Song, Ci; Keefe, Joshua; Mendelson, Michael; Huan, Tianxiao; Sun, Benjamin B.; Laser, Annika; Maranville, Joseph C.; Wu, Hongsheng; Ho, Jennifer E.; Courchesne, Paul; Lyass, Asya; Larson, Martin G.; Gieger, Christian; Graumann, Johannes; Johnson, Andrew D.; Danesh, John; Runz, Heiko; Hwang, Shih Jen; Liu, Chunyu; Butterworth, Adam S.; Suhre, Karsten; Levy, Daniel.

In: Nature Communications, Vol. 9, No. 1, 3268, 01.12.2018.

Research output: Contribution to journalArticle

Yao, C, Chen, G, Song, C, Keefe, J, Mendelson, M, Huan, T, Sun, BB, Laser, A, Maranville, JC, Wu, H, Ho, JE, Courchesne, P, Lyass, A, Larson, MG, Gieger, C, Graumann, J, Johnson, AD, Danesh, J, Runz, H, Hwang, SJ, Liu, C, Butterworth, AS, Suhre, K & Levy, D 2018, 'Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease', Nature Communications, vol. 9, no. 1, 3268. https://doi.org/10.1038/s41467-018-05512-x
Yao, Chen ; Chen, George ; Song, Ci ; Keefe, Joshua ; Mendelson, Michael ; Huan, Tianxiao ; Sun, Benjamin B. ; Laser, Annika ; Maranville, Joseph C. ; Wu, Hongsheng ; Ho, Jennifer E. ; Courchesne, Paul ; Lyass, Asya ; Larson, Martin G. ; Gieger, Christian ; Graumann, Johannes ; Johnson, Andrew D. ; Danesh, John ; Runz, Heiko ; Hwang, Shih Jen ; Liu, Chunyu ; Butterworth, Adam S. ; Suhre, Karsten ; Levy, Daniel. / Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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