Genetic relations between type 1 diabetes, coronary artery disease and leukocyte counts
Authors' conclusion
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.
Study context
- Population
- GWAS summary statistics: leukocyte counts (335,855 healthy individuals), T1D (18,942 cases, 501,638 controls), coronary artery disease (CAD) (122,733 cases, 424,528 controls)GWAS summary statistics
- Outcome
- Genetic correlations and causal relationships between T1D, CAD and leukocyte counts
Methodological detailslinkage disequilibrium score regression, ρ-HESS local genetic correlation, latent causal variable model, GWAS summary statistics
- Linkage disequilibrium score regression
- ρ-HESS local genetic correlation
- Latent causal variable model
- GWAS summary statistics
Main finding
As reported in the abstract
- Genome-wide genetic correlation T1D–CAD (rg)
- 0.088, p=8.60 × 10-3
- Eosinophil count rg(T1D)
- 0.093, p=7.20 × 10-3
- Eosinophil count rg(CAD)
- 0.092, p=3.68 × 10-6
- Lymphocyte count rg(T1D)
- −0.052, p=2.76 × 10-2
- Lymphocyte count rg(CAD)
- 0.176, p=1.82 × 10-15
- Independent loci with Bonferroni-significant local genetic correlations between leukocyte counts, T1D and/or CAD
- 16
- Shared-loci genes whose cis-regulated expression was associated with T1D, CAD and leukocyte counts
- SH2B3, CTSH, MORF4L1, CTRB1, CTRB2, CFDP1, IFIH1
- Genetically predicted lymphocyte count, OR for T1D
- 0.67, p=2.02-19
- Genetically predicted lymphocyte count, OR for CAD
- 1.09, p=2.67 × 10-6
- Genetically predicted neutrophil count, OR for T1D
- 0.82, p=5.63 × 10-5
- Genetically predicted neutrophil count, OR for CAD
- 1.17, p=5.02 × 10-14
- Genetically predicted eosinophil count, OR for T1D
- 1.67, p=5.45 × 10-25
- Genetically predicted eosinophil count, OR for CAD
- 1.07, p=2.03 × 10-4
- Genetic causality proportion T1D–CAD (latent causal variable (LCV)), suggesting a possible intermediary causal variable
- 0.36 ± 0.16, pLCV=1.30 × 10-2
Original publication
Genetic relations between type 1 diabetes, coronary artery disease and leukocyte counts. Diabetologia. Published 14 August 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →