Genomic approach to investigate air pollution's causal impact on neurodevelopment and mental health: An extensive-scale 2-sample Mendelian randomization study.

Genetically proxied higher PM2.5 exposure was associated with lower intelligence and cognitive performance.

• Exposure was assessed using large-scale GWAS data with PM2.5 as an ambient air pollutant exposure.
• The association was identified through 2-sample Mendelian randomization using genetic variants as instrumental variables.
• PM2.5 exposure showed associations across multiple cognitive domains including intelligence scores and cognitive performance measures.
• This finding was robust to the use of MR methodology designed to minimize residual confounding and reverse causation.

Genetically proxied higher PM2.5 exposure was associated with reduced educational attainment.

• Educational attainment was included as one of 17 GWAS datasets across 6 outcome domains.
• The relationship was examined using 2-sample MR with GWAS summary statistics.
• PM2.5 was among the ambient air pollutants assessed alongside PM10, PM2.5-10, NO2, and NOx.
• Self-reported 'very dusty' workplace exposure was also independently associated with poorer educational attainment.

Genetically proxied higher PM2.5 exposure was associated with increased risks of schizophrenia, depression, panic attacks, and vulnerability during youth.

• Psychiatric disorders were one of six outcome domains assessed, alongside emotional and behavioral disorders in children and adolescents.
• The study used 17 GWAS datasets to cover neurodevelopmental and mental health outcomes.
• Vulnerability during youth was included as an outcome in the emotional and behavioral disorders domain.
• These associations were identified using MR methodology to strengthen causal inference beyond observational findings.

Elevated NOx exposure was associated with poorer cognition, lower educational attainment, and increased risks of anxiety, panic disorder, and ADHD.

• NOx was assessed as one of five ambient air pollutants alongside PM2.5, PM10, PM2.5-10, and NO2.
• ADHD was specifically included as one of the six outcome domains investigated.
• Anxiety and panic disorder were captured within the psychiatric disorders outcome domain.
• The MR framework used GWAS-derived genetic variants as instrumental variables for causal inference.

Higher NO2 levels were associated with an increased risk of schizophrenia and higher neuroticism scores.

• NO2 was assessed as one of five ambient air pollutants in the study.
• Neuroticism was included as one of the six outcome domains examined across 17 GWAS datasets.
• Schizophrenia was captured within the psychiatric disorders outcome domain.
• Associations were identified using 2-sample MR with large-scale GWAS data.

Self-reported 'very dusty' workplace exposure was associated with poorer cognitive performance and educational attainment.

• Workplace-related air pollution included three exposures: self-reported 'very dusty' workplace, chemical or other fumes, and diesel exhaust.
• These workplace exposures were assessed alongside five ambient air pollutants in the same MR framework.
• The 'very dusty' workplace exposure showed associations specifically with cognitive and educational outcomes.
• Workplace exposures were self-reported measures used as GWAS-derived exposure proxies.

Chemical fumes and diesel exhaust workplace exposures were linked to reduced academic achievement and increased risks of selected psychiatric outcomes.

• Chemical or other fumes and diesel exhaust were two of three workplace-related air pollution exposures assessed.
• Academic achievement was captured within the educational attainment outcome domain.
• Psychiatric outcomes were among the six domains examined, including psychiatric disorders and emotional/behavioral disorders.
• These findings extend the causal evidence for air pollution's mental health effects to occupational exposure contexts.

The study design used 2-sample Mendelian randomization with large-scale GWAS data to investigate causal effects of air pollution on neurodevelopmental and mental health outcomes.

• Exposures included 5 ambient air pollutants (PM2.5, PM10, PM2.5-10, NO2, and NOx) and 3 workplace-related exposures.
• Outcomes comprised 17 GWAS datasets across 6 domains: cognitive function and intelligence, educational attainment, psychiatric disorders, emotional and behavioral disorders in children and adolescents, ADHD, and neuroticism.
• MR uses genetic variants as instrumental variables to offer a framework to strengthen causal inference regarding neurological effects of air pollution.
• The approach was designed to address limitations of observational studies, which are vulnerable to residual confounding and reverse causation.