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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.
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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.
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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
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Matthew T. Oetjens,

Department of Genetics, University of Michigan, Ann Arbor, MI, US
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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
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Nancy J. Brown,

Department of Medicine, Vanderbilt University Medical School, Nashville, TN, US
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Melinda C. Aldrich,

Department of Thoracic Surgery and Division of Epidemiology, Vanderbilt University Medical School, Nashville, TN, US
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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
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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
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Published on 01 Jun 2017.
Peer Reviewed

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