White blood cells and type 2 diabetes: A Mendelian randomization study

Area of Science:

• Genetics
• Epidemiology
• Metabolic Diseases

Background:

• Observational studies suggest a link between white blood cell (WBC) subtypes and type 2 diabetes (T2D) risk.
• The causal nature of this association remains unclear.

Purpose of the Study:

• To investigate the potential causal effect of WBC subtypes on T2D risk.
• To examine the causal relationship between WBC subtypes and key glycemic traits.

Main Methods:

• Mendelian randomization (MR) analysis utilizing summary statistics from large genome-wide association studies.
• Included neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts.
• Assessed T2D, fasting glucose (FG), glycosylated hemoglobin (HbA1c), and homeostatic model assessment-estimated insulin resistance (HOMA-IR).

Main Results:

• No causal association was found between genetically determined WBC subtypes and T2D risk.
• Consistent findings across univariable, multivariable, and pleiotropy-robust MR methods.
• No evidence of reverse causation from T2D to WBC subtypes, nor causal effects on FG, HbA1c, or HOMA-IR.

Conclusions:

• White blood cells do not play a causal role in the development of insulin resistance or T2D.
• The observed association between WBCs and T2D may be attributed to residual confounding.