Sex-Specific Basal Metabolic Rate and NAFLD Risk: The Multi-Population Observational and Mendelian Randomization...

The impact of basal metabolic rate (BMR) on non-alcoholic fatty liver disease (NAFLD) is still not fully understood, particularly regarding potential sex differences. We aimed to explore population-specific associations using data from health examinations, NHANES 2017-2020, and genome-wide association studies (GWASs).

30,845 Chinese from health examinations and 5019 US adults from NHANES were analyzed. BMR was estimated using the Mifflin-St Jeor equation. Multivariable-adjusted logistic regression and restricted cubic splines (RCS) were applied. To determine the causality, a two-sample MR study was conducted among Europeans using GWASs data for BMR (IEU OpenGWAS) and NAFLD (FinnGen). Odds ratios (ORs) with 95% confidence intervals (CIs) were reported.

In Chinese, ORs (95% CIs) for NAFLD across ascending quartile groups of BMR were 1 (reference), 1.17 (1.03-1.33), 1.83 (1.60-2.09), and 5.98 (4.92-7.28). The corresponding ORs (95% CIs) were 2.00 (1.67-2.39), 2.71 (2.24-3.29), and 4.91 (3.97-6.10) for males, and 1.64 (1.41-1.92), 1.93 (1.64-2.27), and 4.04 (3.41-4.81) for females. In the NHANES, weighted ORs (95% CIs) for NAFLD across quartile groups were 1 (reference), 1.84 (0.95-3.54), 4.98 (2.28-10.89), and 16.10 (6.69-38.72), with similar associations across sexes. Significant sex differences in BMR-NAFLD associations (P for interaction <0.05) were observed in the Chinese, but not in the US population. RCS revealed nonlinear dose-response relationships in both sexes within the Chinese population. Two-sample MR confirmed a causal effect with OR (95% CI) of 1.59 (1.24-2.03).

A higher BMR is an independent and causally relevant risk factor for NAFLD. The observed sex effect modification in the Chinese population suggests that population-specific management strategies may be warranted.