Proteomic analysis of diabetes genetic risk scores identifies complement C2 and neuropilin-2 as predictors of type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study
Authors' conclusion
Identified proteins may represent viable intervention or pharmacological targets to prevent, reverse or slow type 2 diabetes progression, and further research is needed to pursue these targets.
Study context
- Population
- ARIC cohort participants; plasma levels of 4870 proteins and genetic risk scores (GRS) of T2D phenotypes (beta cell function, insulin resistance, lipodystrophy, BMI/blood lipid abnormalities, composite)
- Participants
- 7,241 vs 1,674
- Exposure
- White vs Black
- Whiten = 7,241
- Blackn = 1,674
- Outcome
- Proteins and pathways through which T2D risk variants may influence pathophysiology (protein–GRS associations)
Methodological detailsdiscovery and replication samples, Bonferroni correction, two-sample Mendelian randomisation
- Discovery and replication samples
- Bonferroni correction
- Two-sample Mendelian randomisation
Main finding
As reported in the abstract
Protein–GRS associations
- Plasma proteins identified in White participants after Bonferroni correction
- 22
- Protein–GRS associations replicated in Black participants
- 10
- Directionally consistent in Black participants
- all but one
Observational data: associations, not effects.
Further findings
Proteins associated with T2D
- Associated with prevalent T2D
- 18 of the 22 proteins
- Associated with incident T2D
- 10 proteins
- Secondary analysis
Two-sample Mendelian randomisation: T2D risk
- Complement C2, inverse variance weighted estimate (may be causally related to greater T2D risk): OR per SD
- 1.65; p=7.0 × 10-3
- Neuropilin-2, inversely associated: OR per SD
- 0.44; p=8.0 × 10-3
Original publication
Proteomic analysis of diabetes genetic risk scores identifies complement C2 and neuropilin-2 as predictors of type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetologia. Published 4 October 2022. doi:10.
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