Single-cell expression and Mendelian randomization analyses identify blood genes associated with lifespan and chronic diseases.
Arnaud ChignonValentin Bon-BaretMarie-Chloé BoulangerZhonglin LiDeborah ArgaudYohan BosseSébastien ThériaultBenoit J ArsenaultPatrick MathieuPublished in: Communications biology (2020)
The human lifespan is a heritable trait, which is intricately linked to the development of disorders. Here, we show that genetic associations for the parental lifespan are enriched in open chromatin of blood cells. By using blood expression quantitative trait loci (eQTL) derived from 31,684 samples, we identified for the lifespan 125 cis- and 559 trans-regulated expressed genes (eGenes) enriched in adaptive and innate responses. Analysis of blood single-cell expression data showed that eGenes were enriched in dendritic cells (DCs) and the modelling of cell ligand-receptor interactions predicted crosstalk between DCs and a cluster of monocytes with a signature of cytotoxicity. In two-sample Mendelian randomization (MR), we identified 16 blood cis-eGenes causally associated with the lifespan. In MR, the majority of cis-eGene-disorder association pairs had concordant effects with the lifespan. The present work underlined that the lifespan is linked with the immune response and identifies eGenes associated with the lifespan and disorders.
Keyphrases
- genome wide
- single cell
- immune response
- dendritic cells
- poor prognosis
- rna seq
- binding protein
- gene expression
- dna methylation
- endothelial cells
- induced apoptosis
- stem cells
- computed tomography
- high throughput
- dna damage
- regulatory t cells
- signaling pathway
- contrast enhanced
- cell therapy
- cell proliferation
- long non coding rna
- mesenchymal stem cells
- peripheral blood
- deep learning