Review
Genetic Effects on the Correlation Structure of CVD Risk Factors: Exome-Wide Data From a Ghanaian Population
Authors:
Nuri Kodaman,
Vanderbilt Genetics Institute, Vanderbilt University Medical School, Nashville, TN; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH; Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, US
About Nuri
N. Kodaman and R. S. Sobota contributed equally to this work.
Rafal S. Sobota,
Vanderbilt Genetics Institute, Vanderbilt University Medical School, Nashville, TN; Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, US
About Rafal S.
N. Kodaman and R. S. Sobota contributed equally to this work.
Folkert W. Asselbergs,
Department of Cardiology, Division Heart and Lungs, UMC (University Medical Center) Utrecht, Utrecht; Durrer Center for Cardiogenetic Research, Netherlands Heart Institute, Utrecht, NL; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, GB
Matthew T. Oetjens,
Department of Genetics, University of Michigan, Ann Arbor, MI, US
Jason H. Moore,
Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH; Department of Biostatistics and Epidemiology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, US
Nancy J. Brown,
Department of Medicine, Vanderbilt University Medical School, Nashville, TN, US
Melinda C. Aldrich,
Department of Thoracic Surgery and Division of Epidemiology, Vanderbilt University Medical School, Nashville, TN, US
Scott M. Williams
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH; Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, US
Abstract
Plasma concentration of plasminogen activator inhibitor-1 (PAI-1) is highly correlated with several cardiovascular disease (CVD) risk factors. It also plays a direct role in CVD, including myocardial infarction and stroke, by impeding the dissolution of thrombi in the blood. Insofar as PAI-1 links CVD's risk factors to its endpoints, genetic variants modulating the relationship between PAI-1 and risk factors may be of particular clinical and biological interest. The high heritability of PAI-1, which has not been explained by genetic association studies, may also, in large part, be due to this relationship with CVD risk factors. Using exome-wide data from 1,032 Ghanaian study participants, we tested for heterogeneity of correlation by genotype between PAI-1 and 4 CVD risk factors (body mass index, triglycerides, mean arterial pressure, and fasting glucose) under the hypothesis that loci involved in the relationship between PAI-1 and other risk factors will also modify their correlational structure. We found more significant heterogeneities of correlation by genotype than we found marginal effects, with no evidence of type I inflation. The most significant result among all univariate and multivariate tests performed in this study was the heterogeneity of correlation between PAI-1 and mean arterial pressure at rs10738554, near SLC24A2, a gene previously associated with high blood pressure in African Americans.
How to Cite:
Kodaman N, Sobota RS, Asselbergs FW, Oetjens MT, Moore JH, Brown NJ, et al.. Genetic Effects on the Correlation Structure of CVD Risk Factors: Exome-Wide Data From a Ghanaian Population. Global Heart. 2017;12(2):133–40. DOI: http://doi.org/10.1016/j.gheart.2017.01.013
Published on
01 Jun 2017.
Peer Reviewed
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