Dietary contributions in the genetic variation of liver fibrosis: a genome-wide association study of fibrosis-4 index in the liver fibrosis development

The fibrosis-4 (FIB-4) index is a non-invasive method to assess the severity of liver fibrosis. The development of liver fibrosis is influenced by genetic predisposition and dietary factors. However, the modulating effect of dietary factors on the genetic susceptibility of liver fibrosis remains unclear. The study aims to investigate the role of dietary factors in modulating the genetic susceptibility of liver fibrosis. Here, we conducted a genome-wide association study (GWAS) of FIB-4 index-directed liver fibrosis risk, adjusted with diet, lifestyle factors, and hepatitis serological markers. The high (N = 1,476) and low (N = 36,735) liver fibrosis risk groups were defined with a FIB-4 > 2.67 and 2.67 (3.8%), indicating high fibrosis risk, occurred predominantly among individuals above 60 years old. The multivariable analysis showed that tea intake is significantly associated with a reduced risk of liver fibrosis. The GWAS adjusted for sex, age, age , dietary factors (tea and coffee consumption, vegetarian preference), lifestyle (alcohol consumption, physical activity), hepatitis serological markers (anti-HCV, HBsAg, HBeAg), and the top ten principal components indicated 25 genome-wide significant signals (p