Soremekun Chisom, Jjingo Daudi, Kateete David, Nash Oyekanmi, Nitsch Dorothea, Nyirenda Moffat, Gill Dipender, Zeggini Eleftheria, Grallert Harald, Peters Annette, Chikowore Tinashe, Batini Chiara, Soremekun Opeyemi, Fatumo Segun
The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda.
Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
Front Pharmacol. 2025 Mar 31;16:1436972. doi: 10.3389/fphar.2025.1436972. eCollection 2025.
Observational studies have identified associations between hematological traits and type-2 diabetes mellitus (T2D). However, it is difficult to infer causal effects due to the potential of confounding. Our study utilizes the Mendelian randomization (MR) approach to address the above limitation and investigate the causal effect of hematological traits such as white blood cell (WBC), platelets (PLT), and red blood cell (RBC) on T2D in individuals of African ancestry.
The participating cohorts included participants of African ancestry in the Blood Cell consortium and the Million Veteran Program dataset. Using GWAS summary statistics, we applied a univariable and multivariable Two-sample MR to estimate the causal relationship between hematological traits and T2D.
In the main IVW MR estimates, genetically predicted levels of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV) were associated with decreased risk of T2D. We also observed a decreased risk of T2D with genetically predicted total WBC count and neutrophil count (NEU), for the WBC traits. The multivariable analysis further supported the direct associations of genetically predicted MCH, MCHC, and MCV levels with a decreased risk of T2D. For the European ancestry, a similar pattern of association was observed for MCH and MCV.
These findings indicate that hematological traits may differentially play a role in the development of T2D and be affected by T2D. However, further research is needed to validate and explore the biological pathways and mechanisms involved in these associations.
观察性研究已确定血液学特征与2型糖尿病（T2D）之间存在关联。然而，由于存在混杂因素，难以推断因果效应。我们的研究采用孟德尔随机化（MR）方法来解决上述局限性，并研究白细胞（WBC）、血小板（PLT）和红细胞（RBC）等血液学特征对非洲裔个体T2D的因果效应。
参与的队列包括血细胞联盟和百万退伍军人计划数据集中的非洲裔参与者。使用全基因组关联研究（GWAS）汇总统计数据，我们应用单变量和多变量双样本MR来估计血液学特征与T2D之间的因果关系。
在主要的逆方差加权（IVW）MR估计中，遗传预测的平均红细胞血红蛋白浓度（MCHC）、平均红细胞血红蛋白含量（MCH）和平均红细胞体积（MCV）水平与T2D风险降低相关。对于白细胞特征，我们还观察到遗传预测的白细胞总数和中性粒细胞计数（NEU）与T2D风险降低有关。多变量分析进一步支持了遗传预测的MCH、MCHC和MCV水平与T2D风险降低之间的直接关联。对于欧洲血统，在MCH和MCV方面观察到类似的关联模式。
这些发现表明，血液学特征可能在T2D的发生中发挥不同作用，并受到T2D的影响。然而，需要进一步研究来验证和探索这些关联中涉及的生物学途径和机制。
