Modifiable traits, healthy behaviours, and leukocyte telomere length: a population-based study in UK Biobank.
Modifiable traits, healthy behaviours, and leukocyte telomere length: a population-based study in UK Biobank.
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DOI：
10.1016/s2666-7568(22)00072-1
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发表时间：
2022-05
影响因子：
13.1
通讯作者：
Samani, Nilesh J
中科院分区：
文献类型：
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作者：
Bountziouka, Vasiliki;Musicha, Crispin;Allara, Elias;Kaptoge, Stephen;Wang, Qingning;Angelantonio, Emanuele Di;Butterworth, Adam S;Thompson, John R;Danesh, John N;Wood, Angela M;Nelson, Christopher P;Codd, Veryan;Samani, Nilesh J
端粒长度与多种与年龄相关的疾病和癌症的风险有关。我们的目的是研究端粒长度在多大程度上可以通过生活方式和行为来改变，以及这种改变是否会产生任何临床后果。在这项基于人群的研究中，我们纳入了来自英国生物银行的参与者，他们拥有白细胞端粒长度 (LTL) 测量值、种族和白细胞计数数据。我们使用现有数据和估算数据，研究了 LTL 与 117 种潜在可改变特征的关联，以及两个健康行为指数，包括吸烟、体力活动、饮食、维持健康体重和酒精摄入量。为了帮助解释，通过将性状 β 系数除以年龄 β 系数，将关联性总结为 LTL 中与年龄相关的变化的等效年数。我们使用孟德尔随机化来测试所选关联的因果关系。我们调查了 LTL 与 22 种疾病的关联是否会因健康行为的数量而改变，以及 LTL 可能在多大程度上介导更健康的行为与更长的预期寿命和更低的冠状动脉疾病风险之间的关联。 422 797 名参与者可用于分析（227 620 [53·8%] 为女性，400 036 [94·6%] 为白人）。 71 个性状显示与 LTL 显着相关（p<4·27 × 10–4），但大多数特征是适度的，相当于 LTL 与年龄相关的变化不到 1 年。在对 17 个具有更强关联性（相当于 LTL 与年龄相关的变化≥2 岁）的特征进行多变量分析时，油性鱼类摄入量、受教育程度和一般健康状况保持了这种程度的显着关联，在估算模型中，步行速度和当前吸烟在这种关联水平上也很显着。孟德尔随机分析表明，教育程度和吸烟行为会影响 LTL。健康行为的两个指数均与 LTL 呈正相关且线性相关，行为最健康的人比行为最不健康的人具有更长的 LTL，相当于约 3·5 岁的 LTL 与年龄相关的变化（p<0·001）。然而，健康行为只能解释 LTL 总变异的不到 0·2%，并且不会显着改变 LTL 与所研究的任何疾病风险之间的关联。更健康的行为与更长的预期寿命或更低的冠状动脉疾病风险之间的关联都不是通过 LTL 来介导的。尽管一些潜在可改变的特征和健康行为与 LTL 具有可量化的关联，至少其中一些可能是因果关系，但这些影响的程度不足以显着改变 LTL 与各种疾病或预期寿命之间的关联。尝试通过生活方式或行为改变来改变端粒长度可能不会带来实质性的临床益处。英国医学研究委员会、英国生物技术和生物科学研究委员会以及英国心脏基金会。
Telomere length is associated with risk of several age-related diseases and cancers. We aimed to investigate the extent to which telomere length might be modifiable through lifestyle and behaviour, and whether such modification has any clinical consequences. In this population-based study, we included participants from UK Biobank who had leukocyte telomere length (LTL) measurement, ethnicity, and white blood cell count data. We investigated associations of LTL with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating between them smoking, physical activity, diet, maintenance of a healthy bodyweight, and alcohol intake, using both available and imputed data. To help interpretation, associations were summarised as the number of equivalent years of age-related change in LTL by dividing the trait β coefficients with the age β coefficient. We used mendelian randomisation to test causality of selected associations. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease might be mediated through LTL. 422 797 participants were available for the analysis (227 620 [53·8%] were women and 400 036 [94·6%] were White). 71 traits showed significant (p<4·27 × 10–4) associations with LTL but most were modest, equivalent to less than 1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to ≥2 years of age-related change in LTL), oily fish intake, educational attainment, and general health status retained a significant association of this magnitude, with walking pace and current smoking being additionally significant at this level of association in the imputed models. Mendelian randomisation analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the most healthy behaviours having longer LTL equivalent to about 3·5 years of age-related change in LTL than those with the least heathy behaviours (p<0·001). However, healthy behaviours explained less than 0·2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of coronary artery disease were substantially mediated through LTL. Although several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy. Attempts to change telomere length through lifestyle or behavioural changes might not confer substantial clinical benefit. UK Medical Research Council, UK Biotechnology and Biological Sciences Research Council, and British Heart Foundation.