AUTHOR=Wang Lin , Zhang Chao , Liang Hao , Zhou Nian , Huang Tianji , Zhao Zenghui , Luo Xiaoji TITLE=Polyunsaturated Fatty Acids Level and Bone Mineral Density: A Two-Sample Mendelian Randomization Study JOURNAL=Frontiers in Endocrinology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.858851 DOI=10.3389/fendo.2022.858851 ISSN=1664-2392 ABSTRACT=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 Mendelian randomization (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 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). There were 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 causal relationship between omega-6 FAs and BMD. Further investigations are still required to elucidate the potential mechanism.