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.

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BibTeX RIS

BibTeX

@article{wagen2026neurodegenerative,
  title = {{Neurodegenerative disease risk associated with gene expression in peripheral monocytes across ancestries}},
  author = {Aaron Z. Wagen and Regina H. Reynolds and Jia Nee Foo and Emil K. Gustavsson and Nicholas W. Wood and Sarah A. Gagliano Taliun and Chris Wallace and Cornelis Blauwendraat and Sonia Gandhi and Mina Ryten},
  journal = {Communications Biology},
  year = {2026},
  month = oct,
  doi = {10.1038/s42003-026-10865-x},
  url = {https://www.nature.com/articles/s42003-026-10865-x},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Neurodegenerative disease risk associated with gene expression in peripheral monocytes across ancestries
AU  - Aaron Z. Wagen
AU  - Regina H. Reynolds
AU  - Jia Nee Foo
AU  - Emil K. Gustavsson
AU  - Nicholas W. Wood
AU  - Sarah A. Gagliano Taliun
AU  - Chris Wallace
AU  - Cornelis Blauwendraat
AU  - Sonia Gandhi
AU  - Mina Ryten
PY  - 2026
DA  - 2026/10/02
JO  - Communications Biology
DO  - 10.1038/s42003-026-10865-x
UR  - https://www.nature.com/articles/s42003-026-10865-x
AB  - 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.
SN  - 2399-3642
ER  -

Abstract

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