Genetics
Associations of hematological traits-related polygenic risk scores with liver function Kyeezu Kim* Hye-Young PARK PARK PARK Department of Social and Preventive Medicine, Sungkyunkwan University School of Medicine
Emerging evidence supports a hematological–hepatic axis linking liver function and blood cell traits. We examined associations between blood cell polygenic risk scores (PRSs) and liver-related phenotypes. We calculated PRSs for 13 hematological traits–red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), platelet, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count (WBC), basophil, eosinophil, lymphocyte, neutrophil, and monocyte–in 6,671 adults. Liver phenotypes included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, and fibrosis-4 (FIB-4) index. We examined associations between hematological PRSs and liver-related phenotypes using multivariable linear and logistic regression, adjusting for sociodemographic, behavioral, and clinical factors and stratifying by sex.
Compared with the lowest tertile, the middle tertile of platelet PRS was inversely associated with ALT and AST (ALT: β = -1.37 AST: β = -0.36, both p = 0.01), whereas the highest tertiles of MCV, MCHC, and eosinophil PRSs were associated with higher ALT (β = 1.02-1.17) and AST levels (β = 0.87-0.99; all p < 0.05). The highest tertiles of platelet and neutrophil PRSs were associated with lower FIB-4 scores (platelet: β = -0.08, neutrophil: β = -0.02; all p ≤ 0.01) and reduced fibrosis severity (platelet PRS: OR = 0.49, p = 0.002) while higher tertiles of Hct, MCH, and MCHC were associated with higher FIB-4 scores (β = 0.015-0.019, p < 0.05). Sex-specific associations were observed, with stronger effects of platelet, eosinophil, and MCH PRSs in men; monocyte PRS was associated only in men, whereas RBC, Hct, Hb, neutrophil, and lymphocyte PRSs were associated only in women. MCV and MCHC showed opposite associations with ALT by sex (both p-interaction < 0.01).
Together, our findings support a trait- and sex-specific genetic link between blood cell traits and liver function.