Abstract：
Studies have highlighted a possible link between air pollution and cerebral small vessel disease (CSVD) imaging markers. However, the exact association and effects of polygenic risk score (PRS) defined genetic susceptibility remains unclear. This cross-sectional study used data from the UK Biobank. Participants aged 40-69 years were recruited between the year 2006 and 2010. The annual average concentrations of NOX, NO2, PM2.5, PM2.5-10, PM2.5 absorbance, and PM10, were estimated, and joint exposure to multiple air pollutants was reflected in the air pollution index (APEX). Air pollutant exposure was classified into the low (T1), intermediate (T2), and high (T3) tertiles. Three CSVD markers were used: white matter hyper-intensity (WMH), mean diffusivity (MD), and fractional anisotropy (FA). The first principal components of the MD and FA measures in the 48 white matter tracts were analysed. The sample consisted of 44,470 participants from the UK Biobank. The median (T1-T3) concentrations of pollutants were as follows: NO2, 25.5 (22.4-28.7) μg/m3; NOx, 41.3 (36.2-46.7) μg/m3; PM10, 15.9 (15.4-16.4) μg/m3; PM2.5, 9.9 (9.5-10.3) μg/m3; PM2.5 absorbance, 1.1 (1.0-1.2) per metre; and PM2.5-10, 6.1 (5.9-6.3) μg/m3. Compared with the low group, the high group\'s APEX, NOX, and PM2.5 levels were associated with increased WMH volumes, and the estimates (95 %CI) were 0.024 (0.003, 0.044), 0.030 (0.010, 0.050), and 0.032 (0.011, 0.053), respectively, after adjusting for potential confounders. APEX, PM10, PM2.5 absorbance, and PM2.5-10 exposure in the high group were associated with increased FA values compared to that in the low group. Sex-specific analyses revealed associations only in females. Regarding the combined associations of air pollutant exposure and PRS-defined genetic susceptibility with CSVD markers, the associations of NO2, NOX, PM2.5, and PM2.5-10 with WMH were more profound in females with low PRS-defined genetic susceptibility, and the associations of PM10, PM2.5, and PM2.5 absorbance with FA were more profound in females with higher PRS-defined genetic susceptibility. Our study demonstrated that air pollutant exposure may be associated with CSVD imaging markers, with females being more susceptible, and that PRS-defined genetic susceptibility may modify the associations of air pollutants.
摘要：
研究强调了空气污染与脑小血管病（CSVD）成像标记之间的可能联系。然而,多基因风险评分(PRS)定义的遗传易感性的确切关联和影响尚不清楚.这项横断面研究使用了英国生物银行的数据。在2006年至2010年之间招募了40-69岁的参与者。NOx的年平均浓度，NO2、PM2.5、PM2.5-10、PM2.5吸光度、和PM10，被估计，空气污染指数（APEX）反映了对多种空气污染物的联合暴露。空气污染物暴露被分类为低(T1)，中间（T2），和高（T3）三分位数。使用了三种CSVD标记：白质高强度（WMH），平均扩散率（MD），和分数各向异性(FA)。分析了48个白质区域中MD和FA测量值的第一主成分。样本由来自英国生物库的44,470名参与者组成。污染物的中位数（T1-T3）浓度如下：NO2，25.5（22.4-28.7）μg/m3；NOx，41.3（36.2-46.7）μg/m3；PM10，15.9（15.4-16.4）μg/m3；PM2.5，9.9（9.5-10.3）μg/m3；PM2.5吸光度，每米1.1（1.0-1.2）；PM2.5-10，6.1（5.9-6.3）微克/立方米。与低组相比，高级组的APEX，NOX,PM2.5水平与WMH量增加有关，估计值（95CI）为0.024（0.003，0.044），0.030(0.010,0.050),和0.032(0.011,0.053),分别,在调整了潜在的混杂因素后。APEX,PM10，PM2.5吸光度，与低组相比，高组的PM2.5-10暴露与FA值增加相关。性别特异性分析显示仅在女性中存在关联。关于空气污染物暴露和PRS定义的遗传易感性与CSVD标记的联合关联，NO2，NOX，具有WMH的PM2.5和PM2.5-10在具有低PRS定义的遗传易感性的女性中更为明显，在PRS定义的遗传易感性较高的女性中，PM10，PM2.5和PM2.5吸光度与FA的关联更为深刻。我们的研究表明，空气污染物暴露可能与CSVD成像标记有关，女性更容易受到影响，PRS定义的遗传易感性可能会改变空气污染物的关联。
