Clemens Wittenbecher, Rafael Cuadrat, Luke Johnston, Fabian Eichelmann, Susanne Jäger, Olga Kuxhaus, Marcela Prada, Fabiola M. Del Greco, Andrew A. Hicks, Per Hoffman, Jan Krumsiek, Frank B. Hu, Matthias B. Schulze
- 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 geneticMetabolic 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.…
Metadaten| Author details: | Clemens WittenbecherORCiD, Rafael CuadratORCiD, Luke JohnstonORCiD, Fabian EichelmannORCiD, Susanne JägerORCiD, Olga Kuxhaus, Marcela Prada, Fabiola M. Del Greco, Andrew A. HicksORCiD, Per HoffmanORCiD, Jan Krumsiek, Frank B. Hu, Matthias B. SchulzeORCiDGND |
|---|
| DOI: | https://doi.org/10.1038/s41467-022-28496-1 |
|---|
| ISSN: | 2041-1723 |
|---|
| Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/35177612 |
|---|
| Title of parent work (English): | Nature communications |
|---|
| Publisher: | Nature Research |
|---|
| Place of publishing: | Berlin |
|---|
| Publication type: | Article |
|---|
| Language: | English |
|---|
| Date of first publication: | 2022/02/17 |
|---|
| Publication year: | 2022 |
|---|
| Release date: | 2024/07/10 |
|---|
| Volume: | 13 |
|---|
| Article number: | 936 |
|---|
| Number of pages: | 13 |
|---|
| Funding institution: | German Federal Ministry of Education and Research [82DZD00302]; State of; Brandenburg [82DZD00302]; European Commission; German Federal Ministry; of Education and Research within the Joint Programming Initiative A; Healthy Diet for a Healthy Life, as part of the ERAHDHL [01EA1704];; German Research Foundation's (DFG) [WI5132/1-1]; Danish Diabetes Academy; Postdoctoral Fellowship |
|---|
| Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
|---|
| Peer review: | Referiert |
|---|
| Publishing method: | Open Access / Gold Open-Access |
|---|
| DOAJ gelistet |
|---|
| License (German): |  CC-BY - Namensnennung 4.0 International |
|---|
