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

BACKGROUND: Environmental 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 li...

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Autores principales: Huang, Shu-Yi, Yang, Yu-Xiang, Chen, Shi-Dong, Li, Hong-Qi, Zhang, Xue-Qing, Kuo, Kevin, Tan, Lan, Feng, Lei, Dong, Qiang, Zhang, Can, Yu, Jin-Tai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290559/
https://www.ncbi.nlm.nih.gov/pubmed/34281550
http://dx.doi.org/10.1186/s12916-021-02030-4
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author Huang, Shu-Yi
Yang, Yu-Xiang
Chen, Shi-Dong
Li, Hong-Qi
Zhang, Xue-Qing
Kuo, Kevin
Tan, Lan
Feng, Lei
Dong, Qiang
Zhang, Can
Yu, Jin-Tai
author_facet Huang, Shu-Yi
Yang, Yu-Xiang
Chen, Shi-Dong
Li, Hong-Qi
Zhang, Xue-Qing
Kuo, Kevin
Tan, Lan
Feng, Lei
Dong, Qiang
Zhang, Can
Yu, Jin-Tai
author_sort Huang, Shu-Yi
collection PubMed
description BACKGROUND: Environmental 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. METHODS: A 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. RESULTS: Out 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. CONCLUSIONS: The 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-021-02030-4.
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spelling pubmed-82905592021-07-21 Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis Huang, Shu-Yi Yang, Yu-Xiang Chen, Shi-Dong Li, Hong-Qi Zhang, Xue-Qing Kuo, Kevin Tan, Lan Feng, Lei Dong, Qiang Zhang, Can Yu, Jin-Tai BMC Med Research Article BACKGROUND: Environmental 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. METHODS: A 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. RESULTS: Out 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. CONCLUSIONS: The 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-021-02030-4. BioMed Central 2021-07-20 /pmc/articles/PMC8290559/ /pubmed/34281550 http://dx.doi.org/10.1186/s12916-021-02030-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Huang, Shu-Yi
Yang, Yu-Xiang
Chen, Shi-Dong
Li, Hong-Qi
Zhang, Xue-Qing
Kuo, Kevin
Tan, Lan
Feng, Lei
Dong, Qiang
Zhang, Can
Yu, Jin-Tai
Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis
title Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis
title_full Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis
title_fullStr Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis
title_full_unstemmed Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis
title_short Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis
title_sort investigating causal relationships between exposome and human longevity: a mendelian randomization analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290559/
https://www.ncbi.nlm.nih.gov/pubmed/34281550
http://dx.doi.org/10.1186/s12916-021-02030-4
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