Genetic evidence supports a causal relationship between air pollution and brain imaging-derived phenotypes

Abstract

BackgroundObservational studies have reported associations between air pollutants and brain imaging-derived phenotypes (IDPs); however, whether this relationship is causal remains uncertain. MethodsWe conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the causal relationships between 5 types of air pollutants (N=423,796 to 456,380 individuals) and 587 reliable IDPs (N=33,224 individuals). Two-step MR was also conducted to assess whether the identified effects are mediated through the modulation of circulating cytokines (N=8293). ResultsWe found genetic evidence supporting the association of nitrogen oxides (NOx) with mean intra-cellular volume fraction (ICVF) in the left uncinate fasciculus (IVW β=-0.42, 95 % CI −0.62 to −0.23, P=1.51×10−5) and mean fractional anisotropy (FA) in the left uncinate fasciculus (IVW β=-0.42, 95 % CI −0.62 to −0.21, P=4.89×10−5). In further two-step MR analyses, we did not find evidence that genetic predictions of any circulating cytokines mediated the association between NOx and IDPs. ConclusionThis study provides evidence for the association between air pollutants and brain IDPs, emphasizing the importance of controlling air pollution to improve brain health.