Causal relationships between genetically predicted particulate air pollutants and neurodegenerative diseases: A two-sample Mendelian randomization study

• Published in: Ecotoxicology and environmental safety 2024-10, Vol.284, p.116960, Article 116960
• Main Authors: Liu, Xinjie, Zhang, Xuening, Chang, Tongmin, Zhao, Zengle, Zhang, Yuan, Yang, Xiaorong, Lu, Ming
• Format: Article
• Language: English
• Subjects: Air Pollutants - analysis; Air Pollution - adverse effects; Alzheimer’s disease; Ambient air pollution; Causal inference; Environmental Exposure - adverse effects; Genome-Wide Association Study; Humans; Mendelian randomization; Mendelian Randomization Analysis; Neurodegenerative diseases; Neurodegenerative Diseases - chemically induced; Neurodegenerative Diseases - epidemiology; Neurodegenerative Diseases - genetics; Particulate air pollution; Particulate Matter - analysis; PM10; PM2.5; United Kingdom
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116960

Accumulating observational studies have linked particulate air pollutants to neurodegenerative diseases (NDDs). However, the causal links and the direction of their associations remain unclear. Therefore, we adopted a two-sample Mendelian randomization (TSMR) design using the GWAS-based genetic instruments of particulate air pollutants (PM2.5 and PM10) from the UK Biobank to explore their causal influence on four common neurodegenerative diseases. Estimates of causative relationships were generated by the Inverse variance weighted (IVW) method with multiple sensitive analyses. The heterogeneity and pleiotropy tests were additionally performed to verify whether our findings were robust. Genetically predicted PM2.5 and PM10 could elevate the occurrence of AD (odds ratio [OR] = 2.22, 95 % confidence interval [CI] 1.53–3.22, PIVW = 2.85×10−5, PFalsediscovery rate[FDR]= 2.85×10−4 and OR = 2.41, 95 % CI: 1.26–4.60, PIVW = 0.008, PFDR=0.039, respectively). The results were robust in sensitive analysis. However, no evidence of causality was found for other NDDs. Our present study suggests that PM2.5 and PM10 have a detrimental effect on AD, which indicates that improving air quality to prevent AD may have pivotal public health implications. •The causal associations between particulate air pollutants and neurodegenerative diseases yield unclear.•Mendelian randomization uses genetic variants to infer causality, effectively avoiding confounders and reverse causation.•The study suggests a causal link between genetically predicted PM2.5and PM10and increased Alzheimer’s disease (AD) risk.