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Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia

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Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia. / Reiner, Alexander P; Hartiala, Jaana; Zeller, Tanja; Bis, Joshua C; Dupuis, Josée; Fornage, Myriam; Baumert, Jens; Kleber, Marcus E; Wild, Philipp S; Baldus, Stephan; Bielinski, Suzette J; Fontes, João D; Illig, Thomas; Keating, Brendan J; Lange, Leslie A; Ojeda, Francisco; Müller-Nurasyid, Martina; Munzel, Thomas F; Psaty, Bruce M; Rice, Kenneth; Rotter, Jerome I; Schnabel, Renate B; Tang, W H Wilson; Thorand, Barbara; Erdmann, Jeanette; Jacobs, David R; Wilson, James G; Koenig, Wolfgang; Tracy, Russell P; Blankenberg, Stefan; März, Winfried; Gross, Myron D; Benjamin, Emelia J; Hazen, Stanley L; Allayee, Hooman; CARDIoGRAM Consortium.

in: HUM MOL GENET, Jahrgang 22, Nr. 16, 15.08.2013, S. 3381-93.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Reiner, AP, Hartiala, J, Zeller, T, Bis, JC, Dupuis, J, Fornage, M, Baumert, J, Kleber, ME, Wild, PS, Baldus, S, Bielinski, SJ, Fontes, JD, Illig, T, Keating, BJ, Lange, LA, Ojeda, F, Müller-Nurasyid, M, Munzel, TF, Psaty, BM, Rice, K, Rotter, JI, Schnabel, RB, Tang, WHW, Thorand, B, Erdmann, J, Jacobs, DR, Wilson, JG, Koenig, W, Tracy, RP, Blankenberg, S, März, W, Gross, MD, Benjamin, EJ, Hazen, SL, Allayee, H & CARDIoGRAM Consortium 2013, 'Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia', HUM MOL GENET, Jg. 22, Nr. 16, S. 3381-93. https://doi.org/10.1093/hmg/ddt189

APA

Reiner, A. P., Hartiala, J., Zeller, T., Bis, J. C., Dupuis, J., Fornage, M., Baumert, J., Kleber, M. E., Wild, P. S., Baldus, S., Bielinski, S. J., Fontes, J. D., Illig, T., Keating, B. J., Lange, L. A., Ojeda, F., Müller-Nurasyid, M., Munzel, T. F., Psaty, B. M., ... CARDIoGRAM Consortium (2013). Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia. HUM MOL GENET, 22(16), 3381-93. https://doi.org/10.1093/hmg/ddt189

Vancouver

Reiner AP, Hartiala J, Zeller T, Bis JC, Dupuis J, Fornage M et al. Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia. HUM MOL GENET. 2013 Aug 15;22(16):3381-93. https://doi.org/10.1093/hmg/ddt189

Bibtex

@article{2ea3a3ba0d974613b2939b1fa41c0fee,
title = "Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia",
abstract = "Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare MPO coding sequence variants that were associated with serum MPO levels (rs28730837, P = 5.21 × 10(-12); rs35897051, P = 3.32 × 10(-8)). A GWAS for plasma MPO levels in 9260 European ancestry subjects identified a chromosome 17q22 region near MPO that was significantly associated (lead SNP rs6503905; P = 2.94 × 10(-12)), but the CFH locus did not exhibit evidence of association with plasma MPO levels. Functional analyses revealed that rs800292 was associated with levels of complement proteins in serum. Variants at chromosome 17q22 also had pleiotropic cis effects on gene expression. In a case-control analysis of ∼80 000 subjects from CARDIoGRAM, none of the identified single-nucleotide polymorphisms (SNPs) were associated with CAD. These results suggest that distinct genetic factors regulate serum and plasma MPO levels, which may have relevance for various acute and chronic inflammatory disorders. The clinical implications for CAD and a better understanding of the functional basis for the association of CFH and MPO variants with circulating MPO levels require further study. ",
keywords = "Adult, African Americans/genetics, Aged, Case-Control Studies, Complement Factor H/genetics, Coronary Artery Disease/genetics, European Continental Ancestry Group/genetics, Female, Gene Expression Regulation, Enzymologic, Genetic Association Studies, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Peroxidase/blood, Polymorphism, Single Nucleotide, Young Adult",
author = "Reiner, {Alexander P} and Jaana Hartiala and Tanja Zeller and Bis, {Joshua C} and Jos{\'e}e Dupuis and Myriam Fornage and Jens Baumert and Kleber, {Marcus E} and Wild, {Philipp S} and Stephan Baldus and Bielinski, {Suzette J} and Fontes, {Jo{\~a}o D} and Thomas Illig and Keating, {Brendan J} and Lange, {Leslie A} and Francisco Ojeda and Martina M{\"u}ller-Nurasyid and Munzel, {Thomas F} and Psaty, {Bruce M} and Kenneth Rice and Rotter, {Jerome I} and Schnabel, {Renate B} and Tang, {W H Wilson} and Barbara Thorand and Jeanette Erdmann and Jacobs, {David R} and Wilson, {James G} and Wolfgang Koenig and Tracy, {Russell P} and Stefan Blankenberg and Winfried M{\"a}rz and Gross, {Myron D} and Benjamin, {Emelia J} and Hazen, {Stanley L} and Hooman Allayee and {CARDIoGRAM Consortium}",
year = "2013",
month = aug,
day = "15",
doi = "10.1093/hmg/ddt189",
language = "English",
volume = "22",
pages = "3381--93",
journal = "HUM MOL GENET",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "16",

}

RIS

TY - JOUR

T1 - Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia

AU - Reiner, Alexander P

AU - Hartiala, Jaana

AU - Zeller, Tanja

AU - Bis, Joshua C

AU - Dupuis, Josée

AU - Fornage, Myriam

AU - Baumert, Jens

AU - Kleber, Marcus E

AU - Wild, Philipp S

AU - Baldus, Stephan

AU - Bielinski, Suzette J

AU - Fontes, João D

AU - Illig, Thomas

AU - Keating, Brendan J

AU - Lange, Leslie A

AU - Ojeda, Francisco

AU - Müller-Nurasyid, Martina

AU - Munzel, Thomas F

AU - Psaty, Bruce M

AU - Rice, Kenneth

AU - Rotter, Jerome I

AU - Schnabel, Renate B

AU - Tang, W H Wilson

AU - Thorand, Barbara

AU - Erdmann, Jeanette

AU - Jacobs, David R

AU - Wilson, James G

AU - Koenig, Wolfgang

AU - Tracy, Russell P

AU - Blankenberg, Stefan

AU - März, Winfried

AU - Gross, Myron D

AU - Benjamin, Emelia J

AU - Hazen, Stanley L

AU - Allayee, Hooman

AU - CARDIoGRAM Consortium

PY - 2013/8/15

Y1 - 2013/8/15

N2 - Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare MPO coding sequence variants that were associated with serum MPO levels (rs28730837, P = 5.21 × 10(-12); rs35897051, P = 3.32 × 10(-8)). A GWAS for plasma MPO levels in 9260 European ancestry subjects identified a chromosome 17q22 region near MPO that was significantly associated (lead SNP rs6503905; P = 2.94 × 10(-12)), but the CFH locus did not exhibit evidence of association with plasma MPO levels. Functional analyses revealed that rs800292 was associated with levels of complement proteins in serum. Variants at chromosome 17q22 also had pleiotropic cis effects on gene expression. In a case-control analysis of ∼80 000 subjects from CARDIoGRAM, none of the identified single-nucleotide polymorphisms (SNPs) were associated with CAD. These results suggest that distinct genetic factors regulate serum and plasma MPO levels, which may have relevance for various acute and chronic inflammatory disorders. The clinical implications for CAD and a better understanding of the functional basis for the association of CFH and MPO variants with circulating MPO levels require further study.

AB - Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 × 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 × 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare MPO coding sequence variants that were associated with serum MPO levels (rs28730837, P = 5.21 × 10(-12); rs35897051, P = 3.32 × 10(-8)). A GWAS for plasma MPO levels in 9260 European ancestry subjects identified a chromosome 17q22 region near MPO that was significantly associated (lead SNP rs6503905; P = 2.94 × 10(-12)), but the CFH locus did not exhibit evidence of association with plasma MPO levels. Functional analyses revealed that rs800292 was associated with levels of complement proteins in serum. Variants at chromosome 17q22 also had pleiotropic cis effects on gene expression. In a case-control analysis of ∼80 000 subjects from CARDIoGRAM, none of the identified single-nucleotide polymorphisms (SNPs) were associated with CAD. These results suggest that distinct genetic factors regulate serum and plasma MPO levels, which may have relevance for various acute and chronic inflammatory disorders. The clinical implications for CAD and a better understanding of the functional basis for the association of CFH and MPO variants with circulating MPO levels require further study.

KW - Adult

KW - African Americans/genetics

KW - Aged

KW - Case-Control Studies

KW - Complement Factor H/genetics

KW - Coronary Artery Disease/genetics

KW - European Continental Ancestry Group/genetics

KW - Female

KW - Gene Expression Regulation, Enzymologic

KW - Genetic Association Studies

KW - Genetic Variation

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Peroxidase/blood

KW - Polymorphism, Single Nucleotide

KW - Young Adult

U2 - 10.1093/hmg/ddt189

DO - 10.1093/hmg/ddt189

M3 - SCORING: Journal article

C2 - 23620142

VL - 22

SP - 3381

EP - 3393

JO - HUM MOL GENET

JF - HUM MOL GENET

SN - 0964-6906

IS - 16

ER -