Tan Li, Zhong Meng-Mei, Zhao Ya-Qiong, Feng Yao, Ye Qin, Hu Jing, Ou-Yang Ze-Yue, Chen Ning-Xin, Su Xiao-Lin, Zhang Qian, Liu Qiong, Yuan Hui, Wang Min-Yuan, Feng Yun-Zhi, Guo Yue
Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Nutr Metab (Lond). 2024 Dec 5;21(1):104. doi: 10.1186/s12986-024-00882-0.
polyunsaturated fatty acids (PUFAs) are a category of fatty acids that contain omega-3 and omega-6 fatty acids, which constitute a substantial portion of the Western diet and are vital for maintaining human wellness. The extent to which circulating PUFAs influence the effects of BMI on leukocyte telomere length (LTL) is unknown. Additionally, the impact of circulating PUFA on LTL remains controversial in observational studies.
Using publicly accessible datasets, a genome-wide association study (GWAS) was carried out to determine genetic association estimates for BMI, circulating PUFAs, and LTL. The circulating PUFAs considered were omega-3 PUFAs (i.e., docosahexaenoic acid (DHA) and total omega-3 PUFAs) and omega-6 PUFAs (i.e., linoleic acid (LA) and total omega-6 PUFAs). Two-sample Mendelian randomization (MR) was used to investigate the causal relationships between BMI and PUFA with LTL. Additionally, we examined whether certain PUFA mediate the impact of BMI on LTL.
None of the evidence supported a causal effect of genetically predicted DHA and total omega-3 PUFA on LTL (DHA: β = 0.001, 95% CI: -0.023 to 0.026, p = 0.926; total omega-3 PUFA: β = 0.008, 95% CI: -0.013 to 0.029, p = 0.466). After conducting sensitivity analyses to account for various models of horizontal pleiotropy, the causal association between higher levels of LA and longer LTL persisted (β = 0.034, 95% CI 0.016 to 0.052, p < 0.001). Adjusting for LA in genetics reduced the effect of BMI on LTL from β = -0.039 (95% CI: -0.058 to -0.020, p < 0.001) to -0.034 (95% CI: -0.054 to -0.014, p < 0.001).
This MR study indicates that an increase in genetically predicted circulating LA levels is associated with longer LTL. Additionally, it appears that circulating LA levels play a role in mediating some of the impact that BMI has on LTL.
多不饱和脂肪酸（PUFAs）是一类包含ω-3和ω-6脂肪酸的脂肪酸，它们在西方饮食中占很大比例，对维持人体健康至关重要。循环中的多不饱和脂肪酸对体重指数（BMI）影响白细胞端粒长度（LTL）的程度尚不清楚。此外，在观察性研究中，循环多不饱和脂肪酸对端粒长度的影响仍存在争议。
利用公开可用的数据集，进行了一项全基因组关联研究（GWAS），以确定BMI、循环多不饱和脂肪酸和端粒长度的遗传关联估计值。所考虑的循环多不饱和脂肪酸为ω-3多不饱和脂肪酸（即二十二碳六烯酸（DHA）和总ω-3多不饱和脂肪酸）和ω-6多不饱和脂肪酸（即亚油酸（LA）和总ω-6多不饱和脂肪酸）。采用两样本孟德尔随机化（MR）方法研究BMI和多不饱和脂肪酸与端粒长度之间的因果关系。此外，我们还研究了某些多不饱和脂肪酸是否介导BMI对端粒长度的影响。
没有证据支持遗传预测的DHA和总ω-3多不饱和脂肪酸对端粒长度有因果效应（DHA：β = 0.001，95%可信区间：-0.023至0.026，p = 0.926；总ω-3多不饱和脂肪酸：β = 0.008，95%可信区间：-0.013至0.029，p = 0.466）。在进行敏感性分析以考虑各种水平多效性模型后，较高水平的亚油酸与较长的端粒长度之间的因果关联仍然存在（β = 0.034，95%可信区间0.016至0.052，p < 0.001）。在遗传学中对亚油酸进行调整后，BMI对端粒长度的影响从β = -0.039（95%可信区间：-0.058至-0.020，p < 0.001）降至-0.034（95%可信区间：-0.054至-0.014，p < 0.001）。
这项孟德尔随机化研究表明，遗传预测的循环亚油酸水平升高与较长的端粒长度相关。此外，循环亚油酸水平似乎在介导BMI对端粒长度的一些影响中起作用。
