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Molecular Epidemiology and Cardiology

Department of Clinical Sciences Lund

PI: J. Gustav Smith

Heart disease is the leading caurse of death globally, olthough major transitions in the spectrum of heart disease have occurred over time. The end-stage of all heart diseases - heart failure - results from insufficient cardiac output for the demands of the body at normal filling pressures. A plethora of biochemical changes have been described in the failing heart, but the molecular mechanisms remain poorly understood and carry potential therapeutic implications. An increasingly important form of heart failure is the non-ischemic form of cardiomyopathy seen in diabetes patients.

This research group seeks to improve understanding of the pathophysiology of heart disease, identify novel therapeutic targets and facilitate precision medicine in cardiovascular medicine. To this end, we leverage big data analysis and model-based experiments drawing on methods from genetic epidemiology, proteomics, metabolomics, functional genomics and population sciences. We have a particular interest in the pathways leading up to end-stage heart failure, diabetes cardiomyopathy, and in the pathobiology of the transplanted heart.

Ten recent publications

1. Nielsen MN, et al. Age-specific trends in incidence, mortality, and comorbidities of heart failure in Denmark, 1995 to 2012. Circulation 2017;135:1214-23.
2. Andell P, et al. Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study. Heart 2017: epub Apr 21.
3. Lindgren MP, et al. Sibling risk of hospitalization for heart failure - a nationwide study. Int J Cardiol 2016;223:379-84.
4. Smith JG, Newton-Cheh C. Genome-wide association studies of late-onset cardiovascular disease. J Mol Cell Cardiol 2015;83:131-141.
5. Wild PS, et al. Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function. J Clin Invest 2017: epub Apr 10.
6. Smith JG et al. Discovery of genetic variation on chromosome 5q22 associated with mortality in heart failure. PLoS Genet 2016;12:e1006034.
7. Mega J, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy. Lancet 2015;385:2264-71.
8. Smith JG, et al. Association of low-density lipoprotein cholesterol-related genetic variants with aortic valve calcium and incident aortic stenosis. JAMA 2014;312:1764-71.
9. Christophersen IE, et al. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nat Genet 2017: epub Apr 17.
10. Smith JG, Gerszten RE. Emerging affinity-based proteomic technologies for large-scale plasma profiling in cardiovascular disease. Circulation 2017;135:1651-64.

Gustav Smith