In general members of Kronenbergs group aim to identify determinants of health and disease related to genetic variability, environmental components and biochemical parameters and to study their physiological or pathophysiological functions. Their phenotypes of interest are complex in nature because of an interplay of these factors and are related to atherosclerosis, diabetes mellitus, metabolic syndrome, cancer, infections and associated intermediate phenotypes such as lipoprotein metabolism and inflammation. The Division of Genetic Epidemiology serves as a bridge between basic and clinical research. They work with genetic-epidemiological methods using association studies of candidate genes as well as hypothesis-free genome-wide association studies and also clinical-epidemiological methods.
Ongoing and recent projects
Patients with chronic kidney disease (CKD) are highly susceptible to recurrent opportunistic infections especially in the urinary and respiratory system. The risk for hospitalizations with infections and risk for death increases markedly with decreased kidney function. Furthermore, patients with advanced CKD and infections have an increased risk for cardiovascular ischemia, congestive heart failure and end-stage kidney disease.
One of the main hypothesis is that genetic variants exist that contribute to the susceptibility of opportunistic infections and especially recurrent infections in these high risk CKD patients. They are currently investigating the number of mitochondrial DNA copies in relation to cardiovascular disease as well as infectious diseases in the German Chronic Kidney Disease (GCKD) study which is a prospectively followed cohort of 5217 patients with impaired kidney function and a glomerular filtration rate between 30 and 60 ml/min/1.73 m². They will furthermore perform a genome-wide association study with endpoints such as hospitalizations due to infections, death due to infections, multiple hospitalizations due to infections and certain subentities of infections. They will furthermore investigate whether the cholesterol efflux capacity from macrophages as a measure of the functionality of the reverse cholesterol transport has an influence on the susceptibility to infectious diseases in CKD patients.
Strong collaborations with the groups of:
Lass-Flörl, Weiss, Orth-Höller, Würzner
Kronenberg F. Aortic valve stenosis: the long and winding road. Eur. Heart J. (in press).
Koller A, Fazzini F, Lamina C, Rantner B, Kollerits B, Stadler M, Klein-Weigel P, Fraedrich G, Kronenberg F. Mitochondrial DNA copy number is associated with all-cause mortality and cardiovascular events in patients with peripheral arterial disease. J. Intern. Med. 287:569-579, 2020.
Kronenberg F. High-density lipoprotein in chronic kidney diseases - the devil is in the detail. J. Am. Soc. Nephrol. 29(5):1356-1371, 2018.
Matsushita K, Ballew SH, Coresh J, Arima H, Arnlov J, Cirillo M, Ebert N, Hiramoto JS, Kimm H, Shlipak MG, Visseren FLJ, Gansevoort RT, Kovesdy CP, Shalev V, Woodward M, Kronenberg F. Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 5:718-728, 2017.
Kollerits B, Lamina C, Huth C, Marques-Vidal P, Kiechl S, Seppala I, Cooper J, Hunt SC, Meisinger C, Herder C, Kedenko L, Willeit J, Thorand B, Dähnhardt D, Stöckl D, Willeit K, Roden M, Rathmann W, Paulweber B, Peters A, Kähönen M, Lehtimäki T, Raitakari OT, Humphries SE, Vollenweider P, Dieplinger H, Kronenberg F. Plasma Concentrations of Afamin Are Associated With Prevalent and Incident Type 2 Diabetes: A Pooled Analysis in More Than 20,000 Individuals. Diabetes Care 40:1386-1393, 2017.
Fazzini F, Lamina C, Fendt L, Schultheiss UT, Kotsis F, Hicks AA, Meiselbach H, Weissensteiner H, Forer L, Krane V, Eckardt KU, Köttgen A and Kronenberg F; and the GCKD Investigators. Mitochondrial DNA copy number is associated with mortality and infections in a large cohort of patients with chronic kidney disease. Kidney Int. 96(2):480-488, 2019.
Coassin S, Erhart G, Weissensteiner H, Eca Guimaraes de AM, Lamina C, Schönherr S, Forer L, Haun M, Losso JL, Köttgen A, Schmidt K, Utermann G, Peters A, Gieger C, Strauch K, Finkenstedt A, Bale R, Zoller H, Paulweber B, Eckardt KU, Hüttenhofer A, Huber LA, Kronenberg F. A novel but frequent variant in LPA KIV-2 is associated with a pronounced Lp(a) and cardiovascular risk reduction. Eur. Heart J. 38:1823-1831, 2017.
Das S, Forer L, Schonherr S, Sidore C, Locke AE, Kwong A, Vrieze SI, Chew EY, Levy S, McGue M, Schlessinger D, Stambolian D, Loh PR, Iacono WG, Swaroop A, Scott LJ, Cucca F, Kronenberg F, Boehnke M, Abecasis GR, Fuchsberger C. Next-generation genotype imputation service and methods. Nat. Genet. 48:1284-1287, 2016.