Wagen Aaron Z, Reynolds Regina H, Foo Jia Nee, Fairbrother-Browne Aine, Gustavsson Emil K, Galgiano-Turin Sarah, Wood Nicholas W, Blauwendraat Cornelis, Gandhi Sonia, Ryten Mina
Department of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
The Francis Crick Institute, 1 Midland Road, London, UK.
bioRxiv. 2024 Nov 22:2024.11.20.624489. doi: 10.1101/2024.11.20.624489.
It is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry specific manner. Here we utilise genome-wide association studies and expression quantitative trait loci from African, East Asian and European ancestries to show that genes causing neurodegeneration are preferentially expressed in innate rather than adaptive immune cells, and that expression of these genes mediates the risk of neurodegenerative disease in monocytes in an ancestry-specific manner.
据推测，对区域环境触发因素作出反应的外周免疫状态会导致中枢神经退行性变。区域特异性基因选择压力要求以特定祖先的方式评估这一假设。在这里，我们利用来自非洲、东亚和欧洲祖先的全基因组关联研究和表达数量性状位点，表明导致神经退行性变的基因优先在先天免疫细胞而非适应性免疫细胞中表达，并且这些基因的表达以特定祖先的方式介导单核细胞中神经退行性疾病的风险。
