Polyunsaturated Fatty Acids Level and Bone Mineral Density: A Two-Sample Mendelian Randomization Study

Abstract

Background: This Mendelian randomization (MR) study aimed to explore the causal relationship between polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).

Methods: We conducted a two-sample MR analysis to figure out if there is any causal effect of PUFAs on BMD through the summary data from the genome-wide association study (GWAS). Relationships were evaluated through inverse variance weighted (IVW), MR-Egger, weighted median, and maximum likelihood methods. The MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test was performed to detect the horizontal pleiotropy.

Results: Our findings revealed that omega-6 fatty acids were negatively related to the TB-BMD (beta-estimate: -0.0515; 95% confidence interval [CI]: -0.0911 to -0.0119; standard error [SE]: 0.0201; p-value: 0.0106). The reverse direction MR analysis showed that TB-BMD was linked to the omega-6 FAs (beta-estimate: -0.0699; 95% CI: -0.1304 to -0.0095; SE: 0.0308; p-value: 0.0265). No statistically significant correlations between PUFAs and BMD were observed after adjusting the interactions between metabolites.

Conclusion: This two-sample MR analyses produced strong and new genomic evidence that there was a causal relationship between omega-6 FAs and BMD. Further investigations are still required to elucidate the potential mechanism.

Keywords: bone mineral density—BMD; mendelian randomization; omega - 3 fatty acids; osteoporosis; polyunsaturated fatty acids - PUFA.