Dataset Information

Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease.

ABSTRACT: Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.

SUBMITTER: Folkersen L

PROVIDER: S-EPMC5393901 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease.

Folkersen Lasse L Fauman Eric E Sabater-Lleal Maria M Strawbridge Rona J RJ Frånberg Mattias M Sennblad Bengt B Baldassarre Damiano D Veglia Fabrizio F Humphries Steve E SE Rauramaa Rainer R de Faire Ulf U Smit Andries J AJ Giral Philippe P Kurl Sudhir S Mannarino Elmo E Enroth Stefan S Johansson Åsa Å Enroth Sofia Bosdotter SB Gustafsson Stefan S Lind Lars L Lindgren Cecilia C Morris Andrew P AP Giedraitis Vilmantas V Silveira Angela A Franco-Cereceda Anders A Tremoli Elena E Gyllensten Ulf U Ingelsson Erik E Brunak Søren S Eriksson Per P Ziemek Daniel D Hamsten Anders A Mälarstig Anders A

PLoS genetics 20170403 4

Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant ...[more]

PMID: 28369058

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Dataset Information

Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease.

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Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease.

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