@article{24133a9d814a4c42af93dafdf47863f8,
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 locus 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.}",
note = "Funding Information: Mice used in this study were produced by Eli Lilly, Inc., and made available to the authors. We are grateful to R. Buchan for technical assistance, to P. Froguel, A. Angius, M. Falchi and M. Schneider for comments on the manuscript, to S. Harding (National Heart and Lung Institute, Imperial College, London) for providing the isolated adult rat cardiac myocytes and to J. Sassard (University of Lyon) for providing DNA from the Lyon rat strains. This work was primarily supported by funding from the UK Department of Health (S.A.C. and H.L.) and the British Heart Foundation (R.S., S.A.C.). In addition, studies were supported by research grants from the Medical Research Council of UK (T.J.A., S.A.C.), the Fondation Leducq (T.J.A., S.A.C., M.B.), the EU EURATools award (T.J.A., S.A.C., N.H., M.P.), the Wellcome Trust (I.G.), the Howard Hughes Medical Institute Research Scholars Program (M.P.), the Grant Agency of the Czech Republic (M.P.), the Ministry of Education of the Czech Republic (M.P., V.K.), the 2003T302 grant of the Netherlands Heart Foundation (Y.M.P), the InterCardiology Institute Netherlands (Y.M.P.), a Rubicon grant from the Netherlands Organisation for Scientific Research (NWO, to B.S.), the Wellcome Trust Functional Genomics Initiative and the Biological Atlas of Insulin Resistance (BAIR) (M.K.K.), the German National Genome Research Network (NGFN2, to N.H.), and the US National Institutes of Health{\textquoteright}s National Eye Institute EY000952 and EY13395 (G.W.C.).",
year = "2008",
month = may,
doi = "10.1038/ng.134",
language = "English (US)",
volume = "40",
pages = "546--552",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "5",
}