First, 64, 52, 63, and 41 SNPs consistent with the MR correlation hypothesis were screened from GWAS data of total PUFA, omega-3, omega-6, and omega-6/3 ratios, respectively. Then, these SNPs were carefully screened according to the independence hypothesis and the exclusivity hypothesis. With knee or hip OA as the outcome, SNPs related to weight or BMI, such as rs114863007, rs4766578, and rs7707394, were excluded. Finally, 23-58 SNPs were selected for MR analysis. The F-statistics of these SNPs were all greater than 10. The SNP list is in Table S1 in supplementary file 1.
The 36 MR results showed no significant risk-increasing or risk-reducing effects of total PUFA, omega-3, omega-6, and omega-6/3 ratios on knee, hip, and hand OA. In heterogeneity detection, after removing SNPs that may affect heterogeneity through multiple MR-Presso detections, some MR analyses still have heterogeneity. We used the random-effects model of IVW in these MR analyses. There was no significant horizontal pleiotropy in all MR Analyses. This suggests that horizontal pleiotropy of SNPs is unlikely to influence the results.
The IVW results of the effect of PUFA on OA (male and female) were as follows: total PUFA-knee OA (OR: 0.97, 95% CI: 0.92-1.02, P=0.283); total PUFA-hip OA (OR: 1.01, 95% CI: 0.93-1.08, P=0.806); total PUFA-hand OA (OR: 0.99, 95% CI: 0.91-1.07, P=0.896); omega 3-knee OA (OR: 1.02, 95% CI: 0.98-1.06, P=0.348); omega 3-hip OA (OR: 1.03, 95% CI: 0.98-1.09, P=0.242); omega 3-hand OA (OR: 0.98, 95% CI: 0.89-1.08, P=0.756); omega 6-knee OA (OR: 0.94, 95% CI: 0.89-1.01, P=0.057); omega 6-hip OA (OR: 1.04, 95% CI: 0.97-1.12, P=0.251); omega 6-hand OA (OR: 0.96, 95% CI: 0.88-1.05, P=0.374); omega 6/3-knee OA (OR: 0.99, 95% CI: 0.95-1.03, P=0.524); omega 6/3-hip OA (OR: 0.97, 95% CI: 0.92-1.04, P=0.447); omega 6/3-hand OA (OR: 0.99, 95% CI: 0.91-1.05, P=0.681). 12 MR results showed that PUFA did not affect the development of OA (male and female). The results of MR‒Egger and weighted median methods, as well as the P-values of heterogeneity detection and polytropy detection are shown in Figure 2.
The IVW results of PUFA on OA in male patients were as follows: total PUFA-knee OA (male) (OR: 0.96, 95% CI: 0.87-1.05, P=0.422); total PUFA-hip OA (male) (OR: 1.11, 95% CI: 0.99-1.24, P=0.061); total PUFA-hand OA (male) (OR: 1.14, 95% CI: 0.96-1.35, P=1.121); omega 3-knee OA (OR: 1.01, 95% CI: 0.89-1.12, P=0.941); omega 3-hip OA (OR: 1.09, 95% CI: 0.96-1.23, P=0.171); omega 3-hand OA (OR: 1.12, 95% CI: 0.91-1.39, P=0.281); omega 6-knee OA (OR: 0.94, 95% CI: 0.85-1.05, P=0.325); omega 6-hip OA (OR: 1.04, 95% CI: 0.91-1.18, P=0.537); omega 6-hand OA (OR: 1.11, 95% CI: 0.91-1.35, P=0.267); omega 6/3-knee OA (OR: 1.04, 95% CI: 0.91-1.20, P=0.513); omega 6/3-hip OA (OR: 0.92, 95% CI: 0.84-1.00, P=0.056); omega 6/3-hand OA (OR: 1.03, 95% CI: 0.79-1.33, P=0.799). The detailed results are shown in Figure 3.
The IVW results of PUFA on OA in female patients were as follows: total PUFA-knee OA (female) (OR: 0.97, 95% CI: 0.91-1.04, P=0.450); total PUFA-hip OA (female) (OR: 0.94, 95% CI: 0.87-1.03, P=0.235); total PUFA-hand OA (female) (OR: 1.01, 95% CI: 0.89-1.13, P=0.906); omega 3-knee OA (OR: 1.04, 95% CI: 0.93-1.15, P=0.462); omega 3-hip OA (OR: 0.97, 95% CI: 0.85-1.11, P=0.716); omega 3-hand OA (OR: 0.95, 95% CI: 0.82-1.11, P=0.586); omega 6-knee OA (OR: 0.95, 95% CI: 0.88-1.02, P=0.211); omega 6-hip OA (OR: 0.94, 95% CI: 0.86-1.03, P=0.249); omega 6-hand OA (OR: 0.95, 95% CI: 0.83-1.09, P=0.508); omega 6/3-knee OA (OR: 1.02, 95% CI: 0.91-1.15, P=0.652); omega 6/3-hip OA (OR: 1.00, 95% CI: 0.84-1.18, P=0.995); omega 6/3-hand OA (OR: 1.16, 95% CI: 0.95-1.41, P=0.129). The detailed results are shown in Figure 4.
The leave-one-out plots showed no significant difference in MR results when single SNP was removed. All funnel plots were generally symmetrical, indicating no marked heterogeneity (supplement file 2). In summary, sensitivity analysis indicates that the MR results of this study are robust.