Single-cell Expression and Mendelian Randomization Analyses Identify Blood Genes Associated with Lifespan and Chronic Diseases

Overview

Journal Commun Biol

Specialty Biology

Date 2020 May 3

PMID 32358504

Citations 7

Authors

Arnaud Chignon

Valentin Bon-Baret

Marie-Chloe Boulanger

Zhonglin Li

Deborah Argaud

Yohan Bosse

Sebastien Theriault

Benoit J Arsenault

Patrick Mathieu

Affiliations

Soon will be listed here.

Abstract

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.

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