Association of air pollutants and osteoporosis risk: The modifying effect of genetic predisposition

Cheng Xu; Zhenkun Weng; Qian Liu; Jin Xu; Jingjia Liang; Wenxiang Li; Jia Hu; Tao Huang; Yong Zhou; Aihua Gu

doi:10.1016/j.envint.2022.107562

Association of air pollutants and osteoporosis risk: The modifying effect of genetic predisposition

Environ Int. 2022 Dec:170:107562. doi: 10.1016/j.envint.2022.107562. Epub 2022 Oct 3.

Authors

Cheng Xu¹, Zhenkun Weng¹, Qian Liu¹, Jin Xu², Jingjia Liang¹, Wenxiang Li¹, Jia Hu³, Tao Huang⁴, Yong Zhou⁵, Aihua Gu⁶

Affiliations

¹ State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing, China.
² State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing, China; Department of Maternal, Child, and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing, China.
³ State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Suzhou Institute of Advanced Study in Public Health, Gusu School, Nanjing Medical University, Suzhou, China; Suzhou Center for Disease Prevention and Control, Suzhou, China.
⁴ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
⁵ CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. Electronic address: zhouyong@sibs.ac.cn.
⁶ State Key Laboratory of Reproductive Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University, Nanjing, China. Electronic address: aihuagu@njmu.edu.cn.

PMID: 36228550
DOI: 10.1016/j.envint.2022.107562

Abstract

Background: Limited studies have examined the association between air pollutants and osteoporosis incidence; however, the results are conflicting. We aimed to quantify the effects of selected air pollutants on osteoporosis risk and explore the modifying effect of genetic predisposition.

Methods: A total of 422,955 subjects who did not have osteoporosis at baseline in the UK Biobank were included from 2006 to 2010. We conducted a Cox proportional hazards model with adjustment for covariates to examine the association between air pollutant scores and individual air pollutants and incident osteoporosis. Furthermore, a polygenic risk score (PRS) of osteoporosis was built and examined to determine whether genetic susceptibility modified the effect of air pollutants on osteoporosis. The relationship between air pollutants and osteoporosis was examined by using a restricted cubic spline (RCS) method.

Results: After confounder adjustment, the results showed a remarkable increase in the risk of osteoporosis with each 10 unit increase in exposure to air pollution (hazard ratio: 1.06, 95 % confidence interval: 1.03-1.08), PM_2.5 (1.94, 1.52-2.48), NO₂ (1.06, 1.02-1.10), and NO_X (1.03, 1.01-1.04). However, no significant association was observed between PM₁₀ or PM_2.5-10 exposure and osteoporosis. Subjects with high air pollutant exposure levels and a high PRS had a noteworthy increase in osteoporosis risk compared to those with low air pollutant exposure levels and a low PRS. Air pollutants and genetic variants exerted additive effects on the risk of osteoporosis. Positive correlations were observed between osteoporosis and PM_2.5 (P < 0.001), NO₂ (P = 0.001), and NOx (P = 0.002) exposure.

Conclusions: Exposure to PM_2.5, NO₂ and NOx was associated with an increase in osteoporosis risk, and this effect was more pronounced in populations with high genetic risk. The association between PM_2.5, NO₂ and NOx exposure and osteoporosis is modified by genetic variations.

Keywords: Additive interaction; Air pollution; Genetic susceptibility; Osteoporosis; Polygenic risk score.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Air Pollutants* / adverse effects
Genetic Predisposition to Disease
Humans

Substances

Air Pollutants

Abstract

Publication types

MeSH terms

Substances

Grants and funding