Genetic relations between type 1 diabetes, coronary artery disease and leukocyte counts.
Autor: | Adebekun J; Yale Center for Molecular and Systems Metabolism, Yale University School of Medicine, New Haven, CT, USA.; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA., Nadig A; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA., Saarah P; Yale Center for Molecular and Systems Metabolism, Yale University School of Medicine, New Haven, CT, USA.; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA., Asgari S; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Kachuri L; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA., Alagpulinsa DA; Yale Center for Molecular and Systems Metabolism, Yale University School of Medicine, New Haven, CT, USA. david.alagpulinsa@yale.edu.; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA. david.alagpulinsa@yale.edu. |
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Jazyk: | angličtina |
Zdroj: | Diabetologia [Diabetologia] 2024 Aug 14. Date of Electronic Publication: 2024 Aug 14. |
DOI: | 10.1007/s00125-024-06247-9 |
Abstrakt: | Aims/hypothesis: Type 1 diabetes is associated with excess coronary artery disease (CAD) risk even when known cardiovascular risk factors are accounted for. Genetic perturbation of haematopoiesis that alters leukocyte production is a novel independent modifier of CAD risk. We examined whether there are shared genetic determinants and causal relationships between type 1 diabetes, CAD and leukocyte counts. Methods: Genome-wide association study summary statistics were used to perform pairwise linkage disequilibrium score regression and heritability estimation from summary statistics (ρ-HESS) to respectively estimate the genome-wide and local genetic correlations, and two-sample Mendelian randomisation to estimate the causal relationships between leukocyte counts (335,855 healthy individuals), type 1 diabetes (18,942 cases, 501,638 control individuals) and CAD (122,733 cases, 424,528 control individuals). A latent causal variable (LCV) model was performed to estimate the genetic causality proportion of the genetic correlation between type 1 diabetes and CAD. Results: There was significant genome-wide genetic correlation (r Conclusions/interpretation: This study sheds light on shared genetic mechanisms underlying type 1 diabetes and CAD, which may contribute to their co-occurrence through regulation of gene expression and leukocyte counts and identifies cellular and molecular targets for further investigation for disease prediction and potential drug discovery. (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) |
Databáze: | MEDLINE |
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