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Analysis of a cardiovascular disease genetic risk score in the Diabetes Heart Study

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Abstract

Aims

It remains unclear whether the high cardiovascular disease (CVD) burden in people with type 2 diabetes (T2D) is associated with genetic variants that contribute to CVD in general populations. Recent studies have examined genetic risk scores of single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies for their cumulative contribution to CVD-related traits. Most analyses combined SNPs associated with a single phenotypic class, e.g., lipids. In the present analysis, we examined a more comprehensive risk score comprised of SNPs associated with a broad range of CVD risk phenotypes.

Methods

The composite risk score was analyzed for potential associations with subclinical CVD, self-reported CVD events, and mortality in 983 T2D-affected individuals of European descent from 466 Diabetes Heart Study (DHS) families. Genetic association was examined using marginal models with generalized estimating equations for subclinical CVD and prior CVD events and Cox proportional hazards models with sandwich-based variance estimation for mortality; analyses were adjusted for age and sex.

Results

An increase in genetic risk score was significantly associated with higher levels of coronary artery calcified plaque (p = 1.23 × 10−4); however, no significant associations with self-reported myocardial infarction and CVD events and all-cause and CVD mortality were observed.

Conclusions

These results suggest that a genetic risk score of SNPs associated with CVD events and risk factors does not significantly account for CVD risk in the DHS, highlighting the limitations of applying current genetic markers for CVD in individuals with diabetes.

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Acknowledgments

The authors thank the other investigators, the staff, and the participants of the DHS study for their valuable contributions. This study was supported by the National Institutes of Health through R01 HL67348 and R01 HL092301 (to DWB), R01 AR48797 (to JJC), and F31 AG044879 (to LMR).

Conflict of interest

None.

Ethical standard

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national, Wake Forest School of Medicine Institutional Review Board) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

Informed consent

Informed consent was obtained from all patients for being included in the study.

Author information

Authors and Affiliations

  1. Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Laura M. Raffield

  2. Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Laura M. Raffield, Amanda J. Cox, Pamela J. Hicks & Donald W. Bowden

  3. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Laura M. Raffield, Amanda J. Cox, Pamela J. Hicks & Donald W. Bowden

  4. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Amanda J. Cox, Pamela J. Hicks & Donald W. Bowden

  5. Department of Radiology, Vanderbilt University Medical Center, Nashville, TN, USA

    J. Jeffrey Carr

  6. Department of Internal Medicine - Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Barry I. Freedman

  7. Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Carl D. Langefeld & Fang-Chi Hsu

  8. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA

    Donald W. Bowden

Authors
  1. Laura M. Raffield
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  2. Amanda J. Cox
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  3. J. Jeffrey Carr
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  4. Barry I. Freedman
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  6. Carl D. Langefeld
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  7. Fang-Chi Hsu
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  8. Donald W. Bowden
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Corresponding author

Correspondence to Donald W. Bowden.

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Raffield, L.M., Cox, A.J., Carr, J.J. et al. Analysis of a cardiovascular disease genetic risk score in the Diabetes Heart Study. Acta Diabetol 52, 743–751 (2015). https://doi.org/10.1007/s00592-015-0720-5

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  • DOI: https://doi.org/10.1007/s00592-015-0720-5

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