Correspondence to Author:  Jie Yang, 

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, No.37 Shi’er Qiao Road, Chengdu, Sichuan, China

Abstract:

Observational studies have emphasized the association of female reproductive factors with non-alcoholic fatty liver disease (NAFLD), however, the causal relationship between them still needs further investigation. The aim of this study was to investigate the genetic correlation between reproductive factors and NAFLD. First, two-sample Mendelian randomization (MR) was performed to estimate the causal associations between age at menarche (AAM), age at natural menopause (ANM), age at first birth (AFB), and NAFLD by using pooled data from the Genome-Wide Association Study (GWAS) from the Genetic Consortium. Causality was tested by a variety of methods including inverse variance weighting (IVW), MR-Egger regression, and weighted median method. Additionally, horizontal pleiotropy was verified using the MR-PRESSO metho. The Univariate MR analysis provided evidence that AAM (OR = 0.82, 95% CI: 0.74-0.91, P < 0.0001, PFDR = 0.0002), AFB (OR = 0.91, 95% CI: 0.83-0.99, P = 0.0286, PFDR = 0.0465) were causally associated with NAFLD risk. In contrast, a causal effect of ANM with NAFLD (OR = 1.01, 95% CI: 0.98-1.04, P = 0.539, PFDR = 0.564) has not been confirmed. Mediation analysis showed that the effect of AAM on NAFLD may be mediated through immune cells (CD25 on switched memory B cell and CD127 on CD28+ CD4-CD8- T cell), with mediation effects accounting for 6.23%, 6.68%, respectively. Our MR analysis suggested a causal effect of reproductive factors on NAFLD development, influenced by AAM, AFB. Early AAM and early AFB increase the risk of NAFLD in women.

Keywords:age at menarche; non-alcoholic fatty liver disease; immune cells; Mendelian randomization

Citation:

Jie Yang. The role of immune cells in mediating the effect of hepatoovarian axis: a mendelian randomization study on ovarian aging and NAFLD. Journal of Immunology 2024.