TY  - JOUR
A1  - Wittenbecher, Clemens
A1  - Cuadrat, Rafael
A1  - Johnston, Luke
A1  - Eichelmann, Fabian
A1  - Jäger, Susanne
A1  - Kuxhaus, Olga
A1  - Prada, Marcela
A1  - Del Greco, Fabiola M.
A1  - Hicks, Andrew A.
A1  - Hoffman, Per
A1  - Krumsiek, Jan
A1  - Hu, Frank B.
A1  - Schulze, Matthias B.
T1  - Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology
JF  - Nature communications
N2  - Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.
Y1  - 2022
U6  - https://doi.org/10.1038/s41467-022-28496-1
SN  - 2041-1723
VL  - 13
PB  - Nature Research
CY  - Berlin
ER  -