A statin-dependent QTL for GATM expression is associated with statin-induced myopathy

Lara M. Mangravite (), Barbara E. Engelhardt, Marisa W. Medina, Joshua D. Smith, Christopher D. Brown, Daniel I. Chasman, Brigham H. Mecham, Bryan Howie, Heejung Shim, Devesh Naidoo, QiPing Feng, Mark J. Rieder, Yii.- Der I. Chen, Jerome I. Rotter, Paul M. Ridker, Jemma C. Hopewell, Sarah Parish, Jane Armitage, Rory Collins, Russell A. Wilke, Deborah A. Nickerson, Matthew Stephens () and Ronald M. Krauss ()
Additional contact information
Lara M. Mangravite: Sage Bionetworks, 1100 Fairview Avenue North
Barbara E. Engelhardt: University of Chicago, 920 East 58th Street, Chicago, Illinois 60637, USA
Marisa W. Medina: Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way
Joshua D. Smith: University of Washington, 3720 15th Avenue Northeast, Seattle, Washington 98195, USA
Christopher D. Brown: University of Pennsylvania, 415 Curie Boulevard, Philadelphia, Pennsylvania 19103, USA
Daniel I. Chasman: Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Drive, Boston, Massachusetts 02115, USA
Brigham H. Mecham: Sage Bionetworks, 1100 Fairview Avenue North
Bryan Howie: University of Chicago, 920 East 58th Street, Chicago, Illinois 60637, USA
Heejung Shim: University of Chicago, 920 East 58th Street, Chicago, Illinois 60637, USA
Devesh Naidoo: Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way
QiPing Feng: Vanderbilt University Medical Center, 23rd Avenue South
Mark J. Rieder: University of Washington, 3720 15th Avenue Northeast, Seattle, Washington 98195, USA
Yii.- Der I. Chen: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, California 90502, USA
Jerome I. Rotter: Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, California 90502, USA
Paul M. Ridker: Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Drive, Boston, Massachusetts 02115, USA
Jemma C. Hopewell: Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
Sarah Parish: Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
Jane Armitage: Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
Rory Collins: Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
Russell A. Wilke: Vanderbilt University Medical Center, 23rd Avenue South
Deborah A. Nickerson: University of Washington, 3720 15th Avenue Northeast, Seattle, Washington 98195, USA
Matthew Stephens: University of Chicago, 920 East 58th Street, Chicago, Illinois 60637, USA
Ronald M. Krauss: Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way

Nature, 2013, vol. 502, issue 7471, 377-380

Abstract: Exploration of the interacting effect of statin exposure and genetic variation on gene expression identifies a cis-eQTL that is differentially associated with expression of the GATM gene, which encodes a rate-limiting enzyme involved in creatine synthesis, and that is associated with incidence of statin-induced myopathy, the major adverse effect of statin treatment.

Date: 2013
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DOI: 10.1038/nature12508

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