Genetic susceptibility modifies the association of long-term air pollution exposure on Parkinson's disease

Yi-Ming Huang; Ya-Hui Ma; Pei-Yang Gao; Xi-Han Cui; Jia-Hui Hou; Hao-Chen Chi; Yan Fu; Zhi-Bo Wang; Jian-Feng Feng; Wei Cheng; Lan Tan; Jin-Tai Yu

doi:10.1038/s41531-024-00633-1

Genetic susceptibility modifies the association of long-term air pollution exposure on Parkinson's disease

NPJ Parkinsons Dis. 2024 Jan 17;10(1):23. doi: 10.1038/s41531-024-00633-1.

Authors

Yi-Ming Huang¹, Ya-Hui Ma², Pei-Yang Gao¹, Xi-Han Cui³, Jia-Hui Hou⁴, Hao-Chen Chi¹, Yan Fu¹, Zhi-Bo Wang⁵, Jian-Feng Feng^{6

7

8

9

10}, Wei Cheng^{3

6

7

8}, Lan Tan¹¹, Jin-Tai Yu¹²

Affiliations

¹ Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
² Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
³ Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200040, China.
⁴ Department of Neurology, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Beijing, China.
⁵ Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, China.
⁶ Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, 200433, China.
⁷ Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Shanghai, 200040, China.
⁸ Fudan ISTBI-ZJNU Algorithm Centre for Brain-Inspired Intelligence, Zhejiang Normal University, Jinhua, 321004, China.
⁹ MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China.
¹⁰ Zhangjiang Fudan International Innovation Center, Shanghai, 200433, China.
¹¹ Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. dr.tanlan@163.com.
¹² Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200040, China. jintai_yu@fudan.edu.cn.

Abstract

Inconsistent findings exist regarding the potential association between polluted air and Parkinson's disease (PD), with unclear insights into the role of inherited sensitivity. This study sought to explore the potential link between various air pollutants and PD risk, investigating whether genetic susceptibility modulates these associations. The population-based study involved 312,009 initially PD-free participants with complete genotyping data. Annual mean concentrations of PM_2.5, PM₁₀, NO₂, and NO_x were estimated, and a polygenic risk score (PRS) was computed to assess individual genetic risks for PD. Cox proportional risk models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the associations between ambient air pollutants, genetic risk, and incident PD. Over a median 12.07-year follow-up, 2356 PD cases (0.76%) were observed. Compared to the lowest quartile of air pollution, the highest quartiles of NO₂ and PM₁₀ pollution showed HRs and 95% CIs of 1.247 (1.089-1.427) and 1.201 (1.052-1.373) for PD incidence, respectively. Each 10 μg/m³ increase in NO₂ and PM₁₀ yielded elevated HRs and 95% CIs for PD of 1.089 (1.026-1.155) and 1.363 (1.043-1.782), respectively. Individuals with significant genetic and PM₁₀ exposure risks had the highest PD development risk (HR: 2.748, 95% CI: 2.145-3.520). Similarly, those with substantial genetic and NO₂ exposure risks were over twice as likely to develop PD compared to minimal-risk counterparts (HR: 2.414, 95% CI: 1.912-3.048). Findings suggest that exposure to air contaminants heightens PD risk, particularly in individuals genetically predisposed to high susceptibility.

Abstract

Grants and funding