Integrating Common Risk Factors with Polygenic Scores Improves the Prediction of Type 2 Diabetes

Abstract

We tested associations between 13 established genetic variants and type 2 diabetes (T2D) in 1371 study participants from the Volga-Ural region of the Eurasian continent, and evaluated the predictive ability of the model containing polygenic scores for the variants associated with T2D in our dataset, alone and in combination with other risk factors such as age and sex. Using logistic regression analysis, we found associations with T2D for the CCL20 rs6749704 (OR = 1.68, PFDR = 3.40 × 10−5), CCR5 rs333 (OR = 1.99, PFDR = 0.033), ADIPOQ rs17366743 (OR = 3.17, PFDR = 2.64 × 10−4), TCF7L2 rs114758349 (OR = 1.77, PFDR = 9.37 × 10−5), and CCL2 rs1024611 (OR = 1.38, PFDR = 0.033) polymorphisms. We showed that the most informative prognostic model included weighted polygenic scores for these five loci, and non-genetic factors such as age and sex (AUC 85.8%, 95%CI 83.7%–87.8%). Compared to the model containing only non-genetic parameters, adding the polygenic score for the five T2D-associated loci showed improved net reclassification (NRI = 37.62%, 1.39 × 10−6). Inclusion of all 13 tested SNPs to the model with age and sex did not improve the predictive ability compared to the model containing five T2D-associated variants (NRI = −17.86, p = 0.093). The five variants associated with T2D in people from the Volga-Ural region are linked to inflammation (CCR5, CCL2, CCL20) and glucose metabolism regulation (TCF7L, ADIPOQ2). Further studies in independent groups of T2D patients should validate the prognostic value of the model and elucidate the molecular mechanisms of the disease development.

Assessment of serum fractalkine level as potential role for complications in splenectomized and non-splenectomized patients with β-thalassemia major

“…Expression of CX3CL1 by human adipocytes and stromal vascular cells has been correlated with obesity, insulin resistance, and diabetic mellitus. 16 Previously it was found that rheumatoid arthritis patients' synovial fluid had higher levels of CX3CL1 than healthy individuals. In rheumatoid arthritis, CX3CL1 drives T celldependent proliferation of synovial fibroblasts.…”

Questions Regarding Variants in ADIPOQ in Maternal Circulating Adipokine Profile in Gestational Diabetes Mellitus [Letter]

“…This study detected polymorphisms that were not included among those playing an important role as a risk factor in a previous report. 2 In addition, we noticed that there were several types of adipokine serums detected in their study, such as adiponectin, adipsin/factor D, lipocalin, total PAI-1, and resistin. 3 However, a previous study stated that circulating aprosin, the adipokine serum, was reviewed as a promising candidate for both novel pharmacological treatment strategies and diagnostic tools in clinical cases of diabetes mellitus.…”

“…In addition, a previous study mentioned that the polymorphism of ADIPOQ rs17366743 was one of the integrating common risk factors, besides CCL20 rs6749704, TCF7L2 rs114758349, and CCL2 rs1024611, associated with the prediction of type 2 diabetes on the Eurasian continent. 2 …”

“…In addition, a previous study mentioned that the polymorphism of ADIPOQ rs17366743 was one of the integrating common risk factors, besides CCL20 rs6749704, TCF7L2 rs114758349, and CCL2 rs1024611, associated with the prediction of type 2 diabetes on the Eurasian continent. 2 The study performed by Tangjittipokin et al was recently read and reviewed by our group. We do feel gratitude towards the authors of this article.…”

Evidence from genetic studies among rs2107538 variant in the CCL5 gene and Saudi patients diagnosed with type 2 diabetes mellitus

“…Diabetes is defined by the World Health Organization (WHO) as a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances in carbohydrate, lipid, and protein metabolism resulting from defects in insulin secretion, insulin action, or a combination of both ( Timasheva et al, 2023 ). According to reports from the International Diabetes Federation, the prevalence of diabetes may continue to rise from 537 million in 2021 to 783 million in 2045 ( Mohammed et al, 2023 ).…”