Genetic insights into dietary patterns, liposome mediation, and osteoporosis risk: a Mendelian randomization study

Abstract

Background: This study examines the indirect causal relationships between dietary habits and osteoporosis, mediated through liposomes, utilizing a two-sample Mendelian randomization (MR) approach. The research leverages genetic variations as instrumental variables to explore the genetic influences on dietary habits, liposomes, and osteoporosis, aiming to unravel the complex interplay between diet, lipid metabolism, and bone health.

Methods: The study utilized genome-wide association studies (GWAS) data for liposomes from Finnish individuals and osteoporosis-related data, alongside dietary factors from the OpenGWAS database. Instrumental variables were selected based on genetic variants associated with these factors, using a strict significance level and linkage disequilibrium threshold. Statistical analysis employed the Inverse Variance Weighted method, weighted median, and mode-based methods within the R environment, complemented by sensitivity analyses to ensure the robustness of the causal inferences.

Results: Findings revealed significant causal relationships between specific dietary components (white rice, cereal, and non-oily fish) and osteoporosis risk, both directly and mediated through changes in liposome levels. Notably, white rice consumption was associated with an increased risk of osteoporosis, while cereal and non-oily fish intake showed protective effects. Further, certain liposomes were identified as mediators in these relationships, suggesting a link between diet, lipid profiles, and bone health.

Conclusion: The study highlights the significant impact of dietary habits on osteoporosis risk, mediated through liposomes. These findings underscore the importance of considering lipidomic profiles in dietary guidance and suggest potential targets for preventing osteoporosis through nutritional interventions.

Keywords: GWAS; Mendelian randomization; causal inference; dietary habits; liposomes; osteoporosis.

Figure 1

Volcano plot representing the causal effects of dietary factors on the risk of osteoporosis. The x-axis (Beta) displays the effect size of each dietary component on osteoporosis risk, while the y-axis (–log10 p) reflects the statistical significance of each association. Points above the horizontal threshold line indicate a statistically significant relationship. Colored points represent the direction of the association: red for an increase (Up), blue for a decrease (Down) in the risk of osteoporosis, and gray for non-significant (Not sig) results.

Figure 2

Forest plot visualizing the Mendelian randomization analysis of the causal relationship between the three dietary factors and the risk of osteoporosis. The plot displays the odds ratios (ORs) and their 95% confidence intervals (CIs) for each dietary factor, estimated using multiple Mendelian randomization methods such as Weighted mode, Weighted median, Simple mode, MR Egger, and Inverse variance weighted, represented by different colored symbols. Points to the right of the vertical line (OR = 1) indicate an increased risk of osteoporosis, while points to the left suggest a potential protective effect against the disease.

Figure 3

(A, B) The causal relationship between cereal intake and liposomes; (C) The causal relationship between cereal intake and 11 positive liposomes.

Figure 4

(A, B) The causal relationship between liposomes and osteoporosis; (C) The causal relationship between 11 positive liposomes and osteoporosis.

Figure 5

This diagram illustrates the Mendelian randomization (MR) analysis pathway evaluating the potential causal relationship between dietary intake and osteoporosis, mediated by specific lipid components in liposomes. A total of 179 liposome types are selected for the study, with a focus on the levels of liposomes containing Phosphatidylcholine (16:1_18:2), determined through MR analysis. The pathway demonstrates the method used to elucidate the mediating factors in the relationship between diet, lipid composition, and osteoporosis risk.