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. / Folkersen, Lasse; Fauman, Eric; Sabater-Lleal, Maria; Strawbridge, Rona J; Frånberg, Mattias; Sennblad, Bengt; Baldassarre, Damiano; Veglia, Fabrizio; Humphries, Steve E; Rauramaa, Rainer; de Faire, Ulf; Smit, Andries J; Giral, Philippe; Kurl, Sudhir; Mannarino, Elmo; Enroth, Stefan; Johansson, Åsa; Enroth, Sofia Bosdotter; Gustafsson, Stefan; Lind, Lars; Lindgren, Cecilia M; Morris, Andrew P; Giedraitis, Vilmantas; Silveira, Angela; Franco-Cereceda, Anders; Tremoli, Elena; Gyllensten, Ulf; Ingelsson, Erik; Brunak, Søren; Eriksson, Per; Ziemek, Daniel; Hamsten, Anders; Mälarstig, Anders.

In: P L o S Genetics, Vol. 13, No. 4, e1006706, 04.2017.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Folkersen, L, Fauman, E, Sabater-Lleal, M, Strawbridge, RJ, Frånberg, M, Sennblad, B, Baldassarre, D, Veglia, F, Humphries, SE, Rauramaa, R, de Faire, U, Smit, AJ, Giral, P, Kurl, S, Mannarino, E, Enroth, S, Johansson, Å, Enroth, SB, Gustafsson, S, Lind, L, Lindgren, CM, Morris, AP, Giedraitis, V, Silveira, A, Franco-Cereceda, A, Tremoli, E, Gyllensten, U, Ingelsson, E, Brunak, S, Eriksson, P, Ziemek, D, Hamsten, A & Mälarstig, A 2017, 'Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease', P L o S Genetics, vol. 13, no. 4, e1006706. https://doi.org/10.1371/journal.pgen.1006706

APA

Folkersen, L., Fauman, E., Sabater-Lleal, M., Strawbridge, R. J., Frånberg, M., Sennblad, B., Baldassarre, D., Veglia, F., Humphries, S. E., Rauramaa, R., de Faire, U., Smit, A. J., Giral, P., Kurl, S., Mannarino, E., Enroth, S., Johansson, Å., Enroth, S. B., Gustafsson, S., ... Mälarstig, A. (2017). Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease. P L o S Genetics, 13(4), [e1006706]. https://doi.org/10.1371/journal.pgen.1006706

Vancouver

Folkersen L, Fauman E, Sabater-Lleal M, Strawbridge RJ, Frånberg M, Sennblad B et al. Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease. P L o S Genetics. 2017 Apr;13(4). e1006706. https://doi.org/10.1371/journal.pgen.1006706

Author

Folkersen, Lasse ; Fauman, Eric ; Sabater-Lleal, Maria ; Strawbridge, Rona J ; Frånberg, Mattias ; Sennblad, Bengt ; Baldassarre, Damiano ; Veglia, Fabrizio ; Humphries, Steve E ; Rauramaa, Rainer ; de Faire, Ulf ; Smit, Andries J ; Giral, Philippe ; Kurl, Sudhir ; Mannarino, Elmo ; Enroth, Stefan ; Johansson, Åsa ; Enroth, Sofia Bosdotter ; Gustafsson, Stefan ; Lind, Lars ; Lindgren, Cecilia M ; Morris, Andrew P ; Giedraitis, Vilmantas ; Silveira, Angela ; Franco-Cereceda, Anders ; Tremoli, Elena ; Gyllensten, Ulf ; Ingelsson, Erik ; Brunak, Søren ; Eriksson, Per ; Ziemek, Daniel ; Hamsten, Anders ; Mälarstig, Anders. / Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease. In: P L o S Genetics. 2017 ; Vol. 13, No. 4.

Bibtex

@article{929d722e6ced4957a58312036a2839e3,
title = "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.",
keywords = "Journal Article",
author = "Lasse Folkersen and Eric Fauman and Maria Sabater-Lleal and Strawbridge, {Rona J} and Mattias Fr{\aa}nberg and Bengt Sennblad and Damiano Baldassarre and Fabrizio Veglia and Humphries, {Steve E} and Rainer Rauramaa and {de Faire}, Ulf and Smit, {Andries J} and Philippe Giral and Sudhir Kurl and Elmo Mannarino and Stefan Enroth and {\AA}sa Johansson and Enroth, {Sofia Bosdotter} and Stefan Gustafsson and Lars Lind and Lindgren, {Cecilia M} and Morris, {Andrew P} and Vilmantas Giedraitis and Angela Silveira and Anders Franco-Cereceda and Elena Tremoli and Ulf Gyllensten and Erik Ingelsson and S{\o}ren Brunak and Per Eriksson and Daniel Ziemek and Anders Hamsten and Anders M{\"a}larstig",
year = "2017",
month = apr,
doi = "10.1371/journal.pgen.1006706",
language = "English",
volume = "13",
journal = "P L o S Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "4",

}

RIS

TY - JOUR

T1 - Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease

AU - Folkersen, Lasse

AU - Fauman, Eric

AU - Sabater-Lleal, Maria

AU - Strawbridge, Rona J

AU - Frånberg, Mattias

AU - Sennblad, Bengt

AU - Baldassarre, Damiano

AU - Veglia, Fabrizio

AU - Humphries, Steve E

AU - Rauramaa, Rainer

AU - de Faire, Ulf

AU - Smit, Andries J

AU - Giral, Philippe

AU - Kurl, Sudhir

AU - Mannarino, Elmo

AU - Enroth, Stefan

AU - Johansson, Åsa

AU - Enroth, Sofia Bosdotter

AU - Gustafsson, Stefan

AU - Lind, Lars

AU - Lindgren, Cecilia M

AU - Morris, Andrew P

AU - Giedraitis, Vilmantas

AU - Silveira, Angela

AU - Franco-Cereceda, Anders

AU - Tremoli, Elena

AU - Gyllensten, Ulf

AU - Ingelsson, Erik

AU - Brunak, Søren

AU - Eriksson, Per

AU - Ziemek, Daniel

AU - Hamsten, Anders

AU - Mälarstig, Anders

PY - 2017/4

Y1 - 2017/4

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1371/journal.pgen.1006706

DO - 10.1371/journal.pgen.1006706

M3 - Journal article

C2 - 28369058

VL - 13

JO - P L o S Genetics

JF - P L o S Genetics

SN - 1553-7390

IS - 4

M1 - e1006706

ER -

ID: 177047769