Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass

Enrico Petretto; Rizwan Sarwar; Ian Grieve; Han Lu; Mande K. Kumaran; Phillip J. Muckett; Jonathan Mangion; Blanche Schroen; Matthew Benson; Prakash P. Punjabi; Sanjay K. Prasad; Dudley J. Pennell; Chris Kiesewetter; Elena S. Tasheva; Lolita M. Corpuz; Megan D. Webb; Gary W. Conrad; Theodore W. Kurtz; Vladimir Kren; Judith Fischer; Norbert Hubner; Yigal M. Pinto; Michal Pravenec; Timothy J. Aitman; Stuart A. Cook

doi:https://doi.org/10.1038/ng.134

Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass

Enrico Petretto, Rizwan Sarwar, Ian Grieve, Han Lu, Mande K. Kumaran, Phillip J. Muckett, Jonathan Mangion, Blanche Schroen, Matthew Benson, Prakash P. Punjabi, Sanjay K. Prasad, Dudley J. Pennell, Chris Kiesewetter, Elena S. Tasheva, Lolita M. Corpuz, Megan D. Webb, Gary W. Conrad, Theodore W. Kurtz, Vladimir Kren, Judith FischerNorbert Hubner, Yigal M. Pinto, Michal Pravenec, Timothy J. Aitman, Stuart A. Cook

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Abstract

Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis

Original language	English
Pages (from-to)	546-552
Journal	Nature Genetics
Volume	40
Issue number	5
DOIs	https://doi.org/10.1038/ng.134
Publication status	Published - 2008

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https://doi.org/10.1038/ng.134

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Petretto, E., Sarwar, R., Grieve, I., Lu, H., Kumaran, M. K., Muckett, P. J., Mangion, J., Schroen, B., Benson, M., Punjabi, P. P., Prasad, S. K., Pennell, D. J., Kiesewetter, C., Tasheva, E. S., Corpuz, L. M., Webb, M. D., Conrad, G. W., Kurtz, T. W., Kren, V., ... Cook, S. A. (2008). Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nature Genetics, 40(5), 546-552. https://doi.org/10.1038/ng.134

@article{0a36397ff85948c49fb04cb4e6ec76e3,

title = "Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass",

abstract = "Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis",

author = "Enrico Petretto and Rizwan Sarwar and Ian Grieve and Han Lu and Kumaran, {Mande K.} and Muckett, {Phillip J.} and Jonathan Mangion and Blanche Schroen and Matthew Benson and Punjabi, {Prakash P.} and Prasad, {Sanjay K.} and Pennell, {Dudley J.} and Chris Kiesewetter and Tasheva, {Elena S.} and Corpuz, {Lolita M.} and Webb, {Megan D.} and Conrad, {Gary W.} and Kurtz, {Theodore W.} and Vladimir Kren and Judith Fischer and Norbert Hubner and Pinto, {Yigal M.} and Michal Pravenec and Aitman, {Timothy J.} and Cook, {Stuart A.}",

year = "2008",

doi = "https://doi.org/10.1038/ng.134",

language = "English",

volume = "40",

pages = "546--552",

journal = "Nature Genetics",

issn = "1061-4036",

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Petretto, E, Sarwar, R, Grieve, I, Lu, H, Kumaran, MK, Muckett, PJ, Mangion, J, Schroen, B, Benson, M, Punjabi, PP, Prasad, SK, Pennell, DJ, Kiesewetter, C, Tasheva, ES, Corpuz, LM, Webb, MD, Conrad, GW, Kurtz, TW, Kren, V, Fischer, J, Hubner, N, Pinto, YM, Pravenec, M, Aitman, TJ & Cook, SA 2008, 'Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass', Nature Genetics, vol. 40, no. 5, pp. 546-552. https://doi.org/10.1038/ng.134

TY - JOUR

T1 - Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass

AU - Petretto, Enrico

AU - Sarwar, Rizwan

AU - Grieve, Ian

AU - Lu, Han

AU - Kumaran, Mande K.

AU - Muckett, Phillip J.

AU - Mangion, Jonathan

AU - Schroen, Blanche

AU - Benson, Matthew

AU - Punjabi, Prakash P.

AU - Prasad, Sanjay K.

AU - Pennell, Dudley J.

AU - Kiesewetter, Chris

AU - Tasheva, Elena S.

AU - Corpuz, Lolita M.

AU - Webb, Megan D.

AU - Conrad, Gary W.

AU - Kurtz, Theodore W.

AU - Kren, Vladimir

AU - Fischer, Judith

AU - Hubner, Norbert

AU - Pinto, Yigal M.

AU - Pravenec, Michal

AU - Aitman, Timothy J.

AU - Cook, Stuart A.

PY - 2008

Y1 - 2008

N2 - Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis

AB - Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis

U2 - https://doi.org/10.1038/ng.134

DO - https://doi.org/10.1038/ng.134

M3 - Article

C2 - 18443592

SN - 1061-4036

VL - 40

SP - 546

EP - 552

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -