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JAMA Netw. Open, Mar 03 2025, 8 (3) | https://doi.org/10.1001/jamanetworkopen.2025.0854
Interaction Between Traffic-Related Air Pollution and Parkinson Disease Polygenic Risk Score
Dayoon Kwon, MPH1; Kimberly C. Paul, PhD2; Cynthia Kusters, PhD1,3,4; Jun Wu, PhD5; Jeff M. Bronstein, MD, PhD2; Christina M. Lill, MD6,7; Matthias Ketzel, PhD8,9; Ole Raachou-Nielsen, PhD8,10; Johnni Hansen, PhD10; Beate Ritz, MD, PhD1,2
1Department of Epidemiology, Fielding School of Public Health, UCLA (University of California, Los Angeles), Los Angeles
2Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles
3Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles
4Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, Los Angeles
5Department of Environmental and Occupational Health, School of Population and Public Health, University of California, Irvine
6Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
7Ageing Epidemiology Research Unit, School of Public Health, Imperial College, London, United Kingdom
8Department of Environmental Science, Aarhus University, Roskilde, Denmark
9Global Centre for Clean Air Research, Department of Civil and Environmental Engineering, University of Surrey, Guildford, United Kingdom
10Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark
Corresponding Author: Beate Ritz, MD, PhD
1Department of Epidemiology, Fielding School of Public Health, UCLA (University of California, Los Angeles), Los Angeles
2Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles
3Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles
4Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, UCLA, Los Angeles
5Department of Environmental and Occupational Health, School of Population and Public Health, University of California, Irvine
6Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
7Ageing Epidemiology Research Unit, School of Public Health, Imperial College, London, United Kingdom
8Department of Environmental Science, Aarhus University, Roskilde, Denmark
9Global Centre for Clean Air Research, Department of Civil and Environmental Engineering, University of Surrey, Guildford, United Kingdom
10Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark
Corresponding Author: Beate Ritz, MD, PhD
Abstract
Importance: Genetic and environmental factors are linked to Parkinson disease (PD), but the role of genetic susceptibility in the association between traffic-related air pollution (TRAP) and PD remains unclear.
Objective: To assess the gene-environment interaction between the polygenic risk score (PRS) for PD and long-term TRAP exposure and to estimate the joint effect with PD risk.
Design, setting, and participants: This population-based case-control study used a meta-analytical assessment of studies conducted in central California and Denmark. The Parkinson Environment and Genes (PEG) study in California (June 1, 2000, to July 31, 2017) included 634 patients with PD and 733 controls; the Parkinson Disease in Denmark (PASIDA) study (January 1, 2006, to December 31, 2017) included 966 patients with PD and 1045 controls. Data were analyzed from July 1 to October 31, 2024.
Exposures: PRS was computed by summing the effect estimates of well-known risk alleles from an existing genome-wide association study's summary statistics using participants' genetic arrays. TRAP exposure was estimated using dispersion models to calculate long-term exposure (10- or 15-year means with a 5-year lag) to traffic-related pollutants (represented by carbon monoxide [CO] levels) at participants' residences.
Main outcomes and measures: The main outcome was diagnosis of PD. Using multivariable logistic regression, PD risk was estimated from interactions between PRS (per SD) and TRAP exposure (per IQR), with joint effects based on low (quartiles 1-3) and high (quartile 4) exposure levels.
Results: A total of 1600 patients with PD (mean [SD] age, 65.1 [9.9] years; 990 [61.9%] male) and 1778 controls (mean [SD] age, 64.5 [10.3] years; 992 [55.8%] male) were included. Meta-analytical estimates suggest that both higher PRS and increased TRAP exposure increased PD risk, with an interaction effect estimate of 1.06 (95% CI, 1.00-1.12). Joint effect analysis indicated that individuals with both high PRS and high TRAP exposure were at greatest risk of PD (odds ratio, 3.05; 95% CI, 2.23-4.19) compared with the reference group with a low PRS and low TRAP exposure, suggesting a synergistic effect.
Conclusions and relevance: In this gene-environment interaction study, a combination of long-term air pollution exposure and genetic susceptibility strongly contributed to the risk of developing PD. Widespread exposure to air pollution makes TRAP an important modifiable risk factor affecting large populations globally, particularly individuals with genetic vulnerability.
Objective: To assess the gene-environment interaction between the polygenic risk score (PRS) for PD and long-term TRAP exposure and to estimate the joint effect with PD risk.
Design, setting, and participants: This population-based case-control study used a meta-analytical assessment of studies conducted in central California and Denmark. The Parkinson Environment and Genes (PEG) study in California (June 1, 2000, to July 31, 2017) included 634 patients with PD and 733 controls; the Parkinson Disease in Denmark (PASIDA) study (January 1, 2006, to December 31, 2017) included 966 patients with PD and 1045 controls. Data were analyzed from July 1 to October 31, 2024.
Exposures: PRS was computed by summing the effect estimates of well-known risk alleles from an existing genome-wide association study's summary statistics using participants' genetic arrays. TRAP exposure was estimated using dispersion models to calculate long-term exposure (10- or 15-year means with a 5-year lag) to traffic-related pollutants (represented by carbon monoxide [CO] levels) at participants' residences.
Main outcomes and measures: The main outcome was diagnosis of PD. Using multivariable logistic regression, PD risk was estimated from interactions between PRS (per SD) and TRAP exposure (per IQR), with joint effects based on low (quartiles 1-3) and high (quartile 4) exposure levels.
Results: A total of 1600 patients with PD (mean [SD] age, 65.1 [9.9] years; 990 [61.9%] male) and 1778 controls (mean [SD] age, 64.5 [10.3] years; 992 [55.8%] male) were included. Meta-analytical estimates suggest that both higher PRS and increased TRAP exposure increased PD risk, with an interaction effect estimate of 1.06 (95% CI, 1.00-1.12). Joint effect analysis indicated that individuals with both high PRS and high TRAP exposure were at greatest risk of PD (odds ratio, 3.05; 95% CI, 2.23-4.19) compared with the reference group with a low PRS and low TRAP exposure, suggesting a synergistic effect.
Conclusions and relevance: In this gene-environment interaction study, a combination of long-term air pollution exposure and genetic susceptibility strongly contributed to the risk of developing PD. Widespread exposure to air pollution makes TRAP an important modifiable risk factor affecting large populations globally, particularly individuals with genetic vulnerability.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-19)
- 국외 연구진
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