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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Pattaro, Cristian ; Teumer, Alexander ; Gorski, Mathias ; [weitere]

Springer Science and Business Media LLC ; 2016

In: Nature Communications Vol. 7, No. 1 ( 2016-01-21)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2016-01-21)

Kurzfassung: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Materialart: Online-Ressource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/ncomms10023

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2016

ZDB Id: 2553671-0

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Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease

Song, Ci ; Burgess, Stephen ; Eicher, John D. ; [weitere]

Ovid Technologies (Wolters Kluwer Health) ; 2017

In: Journal of the American Heart Association Vol. 6, No. 6 ( 2017-11-06)

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In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 6 ( 2017-11-06)

Kurzfassung: Plasminogen activator inhibitor type 1 ( PAI ‐1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI ‐1 levels are associated with increased risk of coronary heart disease ( CHD ). However, it is unclear whether the association reflects a causal influence of PAI ‐1 on CHD risk. Methods and Results To evaluate the association between PAI ‐1 and CHD , we applied a 3‐step strategy. First, we investigated the observational association between PAI ‐1 and CHD incidence using a systematic review based on a literature search for PAI ‐1 and CHD studies. Second, we explored the causal association between PAI ‐1 and CHD using a Mendelian randomization approach using summary statistics from large genome‐wide association studies. Finally, we explored the causal effect of PAI ‐1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta‐analysis, the highest quantile of blood PAI ‐1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age‐ and sex‐adjusted model. The effect size was reduced in studies using a multivariable‐adjusted model (odds ratio=1.46; 95% CI : 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI ‐1 level on CHD risk (odds ratio=1.22 per unit increase of log‐transformed PAI ‐1; 95% CI : 1.01, 1.47). In addition, we also detected a causal effect of PAI ‐1 on elevating blood glucose and high‐density lipoprotein cholesterol. Conclusions Our study indicates a causal effect of elevated PAI ‐1 level on CHD risk, which may be mediated by glucose dysfunction.

Materialart: Online-Ressource

ISSN: 2047-9980

URL: Article

DOI: 10.1161/JAHA.116.004918

Sprache: Englisch

Verlag: Ovid Technologies (Wolters Kluwer Health)

Publikationsdatum: 2017

ZDB Id: 2653953-6

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Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Winkler, Thomas W. ; Justice, Anne E. ; Graff, Mariaelisa ; [weitere]

Public Library of Science (PLoS) ; 2016

In: PLOS Genetics Vol. 12, No. 6 ( 2016-6-29), p. e1006166-

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In: PLOS Genetics, Public Library of Science (PLoS), Vol. 12, No. 6 ( 2016-6-29), p. e1006166-

Materialart: Online-Ressource

ISSN: 1553-7404

URL: Article

DOI: 10.1371/journal.pgen.1006166

DOI: 10.1371/journal.pgen.1006166.s001

Sprache: Englisch

Verlag: Public Library of Science (PLoS)

Publikationsdatum: 2016

ZDB Id: 2186725-2

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The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Winkler, Thomas W. ; Justice, Anne E. ; Graff, Mariaelisa ; [weitere]

Public Library of Science (PLoS) ; 2015

In: PLOS Genetics Vol. 11, No. 10 ( 2015-10-1), p. e1005378-

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In: PLOS Genetics, Public Library of Science (PLoS), Vol. 11, No. 10 ( 2015-10-1), p. e1005378-

Materialart: Online-Ressource

ISSN: 1553-7404

URL: Article

DOI: 10.1371/journal.pgen.1005378

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Sprache: Englisch

Verlag: Public Library of Science (PLoS)

Publikationsdatum: 2015

ZDB Id: 2186725-2

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Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Wain, Louise V ; LifeLines Cohort Study ; Verwoert, Germaine C ; [weitere]

Springer Science and Business Media LLC ; 2011

In: Nature Genetics Vol. 43, No. 10 ( 2011-10), p. 1005-1011

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In: Nature Genetics, Springer Science and Business Media LLC, Vol. 43, No. 10 ( 2011-10), p. 1005-1011

Materialart: Online-Ressource

ISSN: 1061-4036 , 1546-1718

URL: Article

DOI: 10.1038/ng.922

RVK:

XA 10000

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2011

ZDB Id: 1494946-5

SSG: 12

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