Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease

Wagen, A. Z.; Reynolds, R. H.; Nee Foo, J.; Fairbrother-Browne, A.; Gustavsson, E. K.; Gagliano-Turin, S. A.; Wood, N. W.; Blauwendraat, C. K.; Gandhi, S.; Ryten, M.

doi:10.1101/2024.11.20.624489

bioRxiv · 10.1101/2024.11.20.624489

Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease

Wagen, A. Z.·Reynolds, R. H.·Nee Foo, J.·Fairbrother-Browne, A.·Gustavsson, E. K.·Gagliano-Turin, S. A.·Wood, N. W.·Blauwendraat, C. K.·Gandhi, S.·Ryten, M.

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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 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.

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Wagen, A. Z., Reynolds, R. H., Nee Foo, J., Fairbrother-Browne, A., Gustavsson, E. K., Gagliano-Turin, S. A., Wood, N. W., Blauwendraat, C. K., Gandhi, S., Ryten, M.. 2024-11-22. Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease. https://doi.org/10.1101/2024.11.20.624489

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