Blood cell counts and nonalcoholic fatty liver disease: Evidence from Mendelian randomization analysis

Figure 1 Mendelian randomization assumptions and study design. Mendelian randomization (MR) analysis relies on three key assumptions. Assumption 1: Genetic variants are closely associated with exposure (blood cell traits); Assumption 2: Genetic variants are not associated with any potential confounders; Assumption 3: Genetic variants are not associated with outcome (liver enzymes and nonalcoholic fatty liver disease) except via exposure. MR: Mendelian randomization; MRPRESSO: Mendelian randomization pleiotropy residual sum and outlier; RBC: Red blood cell count; HGB: Haemoglobin concentration; HCT: Haematocrit; MCH: Mean corpuscular haemoglobin; MCV: Mean corpuscular volume; MCHC: Mean corpuscular haemoglobin concentration; RDW: Red cell distribution width; WBC: White blood cell count; NEU: Neutrophil count; LYM: Lymphocyte count; MONO: Monocyte count; BASO: Basophil count; EO: Eosinophil count; PLT: Platelet count; MPV: Mean platelet volume; RET: Reticulocyte count; RET%: Reticulocyte fraction of red cells; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; AST: Aspartate aminotransferase; NAFLD: Nonalcoholic fatty liver disease. Created with BioRender.com.

Figure 2 Associations of genetically predicted blood cell counts with the risk of nonalcoholic fatty liver disease in the discovery, replication, and combined datasets. OR: Odds ratio; RBC: Red blood cell count; HGB: Haemoglobin concentration; HCT: Haematocrit; MCH: Mean corpuscular haemoglobin; MCV: Mean corpuscular volume; MCHC: Mean corpuscular haemoglobin concentration; RDW: Red cell distribution width; WBC: White blood cell count; NEU: Neutrophil count; LYM: Lymphocyte count; MONO: Monocyte count; BASO: Basophil count; EO: Eosinophil count; PLT: Platelet count; MPV: Mean platelet volume; RET: Reticulocyte count; RET%: Reticulocyte fraction of red cells; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; AST: Aspartate aminotransferase; NAFLD: Nonalcoholic fatty liver disease.

Figure 3 Inverse-variance weighted–Mendelian randomization results before and after correcting for waist-to-hip ratio and type 2 diabetes using the multivariable Mendelian randomization framework. A: Blood cell counts associated liver enzyme; B: Blood cell counts associated liver enzyme. OR: Odds ratio; RBC: Red blood cell count; HGB: Haemoglobin concentration; HCT: Haematocrit; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; AST: Aspartate aminotransferase; NAFLD: Nonalcoholic fatty liver diseases; T2D: Type 2 diabetes.