目的:动物模型提示ω-3多不饱和脂肪酸(PUFAs)可能通过调节脉络膜血流灌注来预防近视,但是临床证据很少而且好坏参半。我们旨在使用孟德尔随机化(MR)分析确定omega-3PUFA与近视之间的因果关系。
方法:双样本MR分析。
方法:暴露是遗传预测的18个脂肪酸(FAs)相关性状。使用球面等效屈光度(SER)和轴向长度作为近视的测量值。关于18个FAs相关性状的血液水平的全基因组关联研究汇总数据(n=115,006),折射球面当量(n=351,091),轴向长度(n=69,945)和脉络膜厚度(n=44,823)来自英国生物库,成人健康和衰老队列的遗传流行病学研究,以及屈光不正和近视研究联盟。我们使用了五个MR模型,如果在至少3个MR模型中Bonferroni校正的P值≤2.78×10-3,则认为结果具有统计学意义。β代表FAs水平每标准偏差单位增加的结果变化(屈光度的SER;以mm为单位的轴向长度;以标准偏差为单位的脉络膜厚度)。
结果:在Bonferroni校正的意义上,更高水平的欧米茄-3(β,0.32-0.34),omega-3/总FAs比率(Beta,0.31-0.44),二十二碳六烯酸(DHA)(β,0.36-0.46),DHA/总FAs比率(β,0.37-0.53),PUFA/总FA比率(Beta,0.07-1.003),和不饱和度(β,0.28-0.44)与更积极的SER相关,提示近视风险较低。轴向长度观察到类似的趋势,尽管具有临界意义(P≤0.035in≥2个模型)。更高水平的omega-3,DHA,DHA/总FAs比率,PUFA/总FA比率,PUFA/单不饱和脂肪酸比率,和不饱和度名义上与较厚的脉络膜厚度相关(β,0.05-0.13;P≤0.045in≥2个型号)。
结论:我们的多个MR模型表明omega-3和DHA对近视有保护作用,可能通过调节脉络膜血液灌注。需要进一步的随机临床试验来确认有效性并确定最佳剂量和持续时间。
OBJECTIVE: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis.
METHODS: Two-sample MR analysis.
METHODS: Exposures are genetically predicted 18 fatty acids (FAs) related traits. Spherical equivalent refraction (SER) and axial length were used as measurements of myopia. Genome-wide association study summary data on blood levels of 18 FAs related traits (n=115,006), refractive spherical equivalent (n=351,091), axial length (n=69,945) and choroidal thickness (n=44,823) were sourced from the UK Biobank, the Genetic Epidemiology Research on Adult Health and Aging cohort, and the Consortium for Refractive Error and Myopia Study. We used five MR models and considered results statistically significant if the Bonferroni-corrected P-value was ≤2.78 × 10-3 in at least 3 MR models. The beta represents the change in outcomes (SER in diopter; axial length in mm; choroidal thickness in standard deviation) per standard deviation unit increase in FAs levels.
RESULTS: At a Bonferroni-corrected significance, higher levels of omega-3 (Beta, 0.32-0.34), omega-3/total FAs ratio (Beta, 0.31-0.44), docosahexaenoic acid (DHA) (Beta, 0.36-0.46), DHA/total FAs ratio (Beta, 0.37-0.53), PUFAs/total FAs ratio (Beta, 0.07-1.003), and degree of unsaturation (Beta, 0.28-0.44) were associated with a more positive SER, suggesting a lower risk of myopia. Similar trends were observed for axial length albeit with borderline significance (P≤0.035 in ≥2 models). Higher levels of omega-3, DHA, DHA/total FAs ratio, PUFAs/total FAs ratio, PUFAs/monounsaturated FAs ratio, and degree of unsaturation were nominally associated with thicker choroidal thickness (Beta, 0.05-0.13; P≤0.045 in ≥2 models).
CONCLUSIONS: Our multiple MR models suggest a protective effect of omega-3 and DHA on myopia, potentially through modulation of choroidal blood perfusion. Further randomized clinical trials are needed to confirm the effectiveness and determine the optimal dose and duration.