Fine Particulate Matter Exposure, Genetic Susceptibility, and the Risk of Incident Stroke: A Prospective Cohort Study

Keyong Huang; Jiajing Jia; Fengchao Liang; Jianxin Li; Xiaoge Niu; Xueli Yang; Shufeng Chen; Jie Cao; Chong Shen; Xiaoqing Liu; Ling Yu; Fanghong Lu; Xianping Wu; Liancheng Zhao; Ying Li; Dongsheng Hu; Jianfeng Huang; Yang Liu; Dongfeng Gu; Fangchao Liu; Xiangfeng Lu

doi:10.1161/STROKEAHA.123.043812

Fine Particulate Matter Exposure, Genetic Susceptibility, and the Risk of Incident Stroke: A Prospective Cohort Study

Stroke. 2024 Jan;55(1):92-100. doi: 10.1161/STROKEAHA.123.043812. Epub 2023 Nov 29.

Authors

Keyong Huang^#^{1

2}, Jiajing Jia^#^{1

2}, Fengchao Liang³, Jianxin Li^{1

2}, Xiaoge Niu^{1

2

4}, Xueli Yang⁵, Shufeng Chen^{1

2}, Jie Cao^{1

2}, Chong Shen^{6

7}, Xiaoqing Liu⁸, Ling Yu⁹, Fanghong Lu¹⁰, Xianping Wu¹¹, Liancheng Zhao^{1

2}, Ying Li^{1

2}, Dongsheng Hu^{1

12

13}, Jianfeng Huang^{1

2}, Yang Liu¹⁴, Dongfeng Gu^{2

15}, Fangchao Liu^{1

2}, Xiangfeng Lu^{1

2}

Affiliations

¹ Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (K.H., J.J., J.L., X.N., S.C., J.C., L.Z., Y. Li, J.H., D.G., F. Liu, X. Lu).
² Key Laboratory of Cardiovascular Epidemiology (K.H., J.J., J.L., S.C., J.C., L.Z., Y. Li, J.H., D.G., F. Liu, X. Lu), Chinese Academy of Medical Sciences, Beijing, China.
³ School of Public Health and Emergency Management (F. Liang), Southern University of Science and Technology, Shenzhen, China.
⁴ Department of Nephrology, Henan Provincial Key Laboratory of Kidney Disease and Immunology, Henan Provincial Clinical Research Center for Kidney Disease, Henan Provincial People's Hospital and People's Hospital of Zhengzhou University, China (X.N.).
⁵ Tianjin Key Laboratory of Environment, Nutrition and Public Health, Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, China (X.Y.).
⁶ Research Units of Cohort Study on Cardiovascular Diseases and Cancers (C.S.), Chinese Academy of Medical Sciences, Beijing, China.
⁷ Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, China (C.S.).
⁸ Division of Epidemiology, Guangdong Provincial People's Hospital and Cardiovascular Institute, Guangzhou, China (X. Liu).
⁹ Department of Cardiology, Fujian Provincial People's Hospital, Fuzhou, China (L.Y.).
¹⁰ Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China (F. Lu).
¹¹ Sichuan Center for Disease Control and Prevention, Chengdu, China (X.W.).
¹² Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, China (D.H.).
¹³ Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, China (D.H.).
¹⁴ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA (Y. Liu).
¹⁵ School of Medicine (D.G), Southern University of Science and Technology, Shenzhen, China.

^# Contributed equally.

PMID: 38018834
DOI: 10.1161/STROKEAHA.123.043812

Abstract

Background: Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors.

Methods: This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM_2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM_2.5 and polygenic risk score with incident stroke and the potential effect modifications.

Results: Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM_2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM_2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM_2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM_2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride.

Conclusions: Long-term exposure to PM_2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.

Keywords: air pollution; genetic association studies; particulate matter; stroke.

MeSH terms

Adult
Air Pollutants* / adverse effects
Air Pollution* / adverse effects
Atrial Fibrillation* / complications
Diabetes Mellitus, Type 2*
Environmental Exposure / adverse effects
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Incidence
Particulate Matter / adverse effects
Particulate Matter / analysis
Prospective Studies
Risk Factors
Stroke* / chemically induced
Stroke* / epidemiology
Stroke* / genetics
Triglycerides

Substances

Particulate Matter
Triglycerides
Air Pollutants