Neurodegenerative disease risk associated with gene expression in peripheral monocytes across ancestries

Abstract

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 causally-implicated in neurodegeneration are preferentially expressed in innate rather than adaptive immune cells. Using colocalisation and Mendelian randomisation analyses, we show that in addition to known colocalising signals in microglia, genetic variants associated with neurodegenerative disease risk also regulate the expression of these genes in peripheral monocytes across ancestries.