Connecting Genomics and Proteomics to Identify Protein Biomarkers for Adult and Youth-Onset Type 2 Diabetes: A Two-Sample Mendelian Randomization Study
posted on 2022-03-02, 15:55authored byFaegheh Ghanbari, Nahid Yazdanpanah, Mojgan Yazdanpanah, J. Brent Richards, Despoina Manousaki
Type 2 diabetes shows an increasing
prevalence in both adults and children. Identification of biomarkers for both
youth and adult-onset type 2 diabetes is crucial for development of screening
tools or drug targets. Here, using two-sample Mendelian randomization (MR), we identified
22 circulating proteins causally linked to adult type 2 diabetes and 11 proteins
with suggestive evidence for association with youth-onset type 2 diabetes. Among
these, co-localization analysis further supported a role in type 2 diabetes for
C-type
Mannose Receptor 2 (MR OR=0.85, 95% CI 0.79 – 0.92 per genetically predicted standard
deviation (SD) increase in protein level), MANS domain containing 4 (MR OR=0.90,
95% CI 0.88 – 0.92), Sodium/potassium-transporting
ATPase subunit Beta-2 (MR OR=1.10, 95% CI 1.06 – 1.15), Endoplasmic
Reticulum Oxidoreductase 1 Beta (MR OR=1.09, 95% CI 1.05 – 1.14),
Spermatogenesis-Associated Protein 20 (MR OR=1.12, 95% CI 1.06 – 1.18),
Haptoglobin (MR OR=0.96, 95% CI 0.94 – 0.98), and Alpha
1-3-N-Acetylgalactosaminyltransferase and Alpha 1-3-Galactosyltransferase (MR OR=1.04,
95% CI 1.03 – 1.05). Our findings support a
causal role in type 2 diabetes for a set of circulating proteins, which represent
promising type 2 diabetes drug targets.
Funding
Pediatric Endocrine Society (PES) Clinical Scholar