Integrative proteogenomic and observational analysis identifies potential biomarkers for latent autoimmune diabetes in adults
Authors' conclusion
This study suggests that CXCL10 is a putative biomarker associated with LADA, demonstrating discriminative ability to distinguish LADA from T2D in an observational clinical cohort. These findings contribute to understanding the autoimmune molecular aetiology of LADA and support its diagnostic potential in resolving the clinical ambiguity between LADA and T2D.
Study context
- Population
- cis-pQTLs for 1,389 plasma proteins (deCODE, n = 35,559); Latent autoimmune diabetes in adults (LADA) genome-wide association study (GWAS) (2,634 cases, 5,947 controls, European ancestry); matched Chinese clinical studymatched Chinese clinical study
- Participants
- 241 participants
- Exposure
- Genetically predicted plasma protein levels and LADA risk; CXCL10 discrimination of LADA vs healthy controls and T2D
- Outcome
- Genetically predicted plasma protein levels and LADA risk
Methodological detailsproteome-wide Mendelian randomisation (MR), colocalisation, multiple sensitivity analyses, phenome-wide MR, matched Chinese clinical study
- Proteome-wide MR
- Colocalisation
- Multiple sensitivity analyses
- Phenome-wide MR
- Matched Chinese clinical study
Main finding
As reported in the abstract
CXCL10, OR [95% CI] per 1-SD increase
5.49
1.74,17.32
Serum amyloid A1 (SAA1), OR [95% CI] per 1-SD increase
1.28
1.14,1.45
SAA2, OR [95% CI] per 1-SD increase
1.22
1.11,1.34
Observational data: associations, not effects.
Further findings
CXCL10 discrimination of LADA from healthy controls
- ROC-AUC
- 0.889
- PR-AUC
- 0.919
- Adequate calibration
CXCL10 discrimination of LADA from T2D
- ROC-AUC
- 0.838
- PR-AUC
- 0.921
- Adequate calibration
Druggability of CXCL10
- CXCL10 a drug target under investigation
Safety
Phenome-wide MR of CXCL10
- No major safety concerns across diseases and traits
- 1,006 diseases and traits
Original publication
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