Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis

BMC Medicine

Hong-Qi Li¹  Qiang Dong¹  Yu-Xiang Yang¹  Shi-Dong Chen¹  Shu-Yi Huang¹  Xue-Qing Zhang¹  Kevin Kuo¹  Jin-Tai Yu¹  Lan Tan²  Lei Feng³  Can Zhang⁴ 

[1] Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, 200040, Shanghai, China;Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China;Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Diseases (MIND), Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA;

关键词: Longevity;    Mendelian randomization;    Exposome;   

DOI  :  10.1186/s12916-021-02030-4

来源: Springer

【 摘 要 】

BackgroundEnvironmental factors are associated with human longevity, but their specificity and causality remain mostly unclear. By integrating the innovative “exposome” concept developed in the field of environmental epidemiology, this study aims to determine the components of exposome causally linked to longevity using Mendelian randomization (MR) approach.MethodsA total of 4587 environmental exposures extracting from 361,194 individuals from the UK biobank, in exogenous and endogenous domains of exposome were assessed. We examined the relationship between each environmental factor and two longevity outcomes (i.e., surviving to the 90th or 99th percentile age) from various cohorts of European ancestry. Significant results after false discovery rates correction underwent validation using an independent exposure dataset.ResultsOut of all the environmental exposures, eight age-related diseases and pathological conditions were causally associated with lower odds of longevity, including coronary atherosclerosis (odds ratio = 0.77, 95% confidence interval [0.70, 0.84], P = 4.2 × 10−8), ischemic heart disease (0.66, [0.51, 0.87], P = 0.0029), angina (0.73, [0.65, 0.83], P = 5.4 × 10−7), Alzheimer’s disease (0.80, [0.72, 0.89], P = 3.0 × 10−5), hypertension (0.70, [0.64, 0.77], P = 4.5 × 10−14), type 2 diabetes (0.88 [0.80, 0.96], P = 0.004), high cholesterol (0.81, [0.72, 0.91], P = 0.0003), and venous thromboembolism (0.92, [0.87, 0.97], P = 0.0028). After adjusting for genetic correlation between different types of blood lipids, higher levels of low-density lipoprotein cholesterol (0.72 [0.64, 0.80], P = 2.3 × 10−9) was associated with lower odds of longevity, while high-density lipoprotein cholesterol (1.36 [1.13, 1.62], P = 0.001) showed the opposite. Genetically predicted sitting/standing height was unrelated to longevity, while higher comparative height size at 10 was negatively associated with longevity. Greater body fat, especially the trunk fat mass, and never eat sugar or foods/drinks containing sugar were adversely associated with longevity, while education attainment showed the opposite.ConclusionsThe present study supports that some age-related diseases as well as education are causally related to longevity and highlights several new targets for achieving longevity, including management of venous thromboembolism, appropriate intake of sugar, and control of body fat. Our results warrant further studies to elucidate the underlying mechanisms of these reported causal associations.

【 授权许可】

CC BY