• Genome-wide host-pathogen analyses reveal genetic interaction points in tuberculosis disease

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Document Title

Genome-wide host-pathogen analyses reveal genetic interaction points in tuberculosis disease

Author

Phelan J. Gomez-Gonzalez P.J. Andreu N. Omae Y. Toyo-Oka L. Yanai H. Miyahara R. Nedsuwan S. de Sessions P.F. Campino S. Sallah N. Parkhill J. Smittipat N. Palittapongarnpim P. Mushiroda T. Kubo M. Tokunaga K. Mahasirimongkol S. Hibberd M.L. Clark T.G.

Affiliations

Faculty of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine London United Kingdom; Department of Human Genetics Graduate School of Medicine The University of Tokyo Tokyo Japan; Fukujuji Hospital and Research Institute of Tuberculosis Japan Anti-Tuberculosis Association Kiyose Japan; Genome Medical Science Project National Center for Global Health and Medicine Tokyo Japan; Chiangrai Prachanukroh Hospital Chiangrai Thailand; Genome Institute of Singapore One North Singapore; Department of Veterinary Medicine University of Cambridge Cambridge United Kingdom; National Center for Genetic Engineering and Biotechnology National Science and Technology Development Agency Pathumthani Thailand; RIKEN Center for Integrative Medical Sciences Yokohama Japan; Medical Genetics Center Medical Life Sciences Institute Department of Medical Sciences Ministry of Public Health Nonthaburi Thailand; Faculty of Epidemiology and Population Health London School of Hygiene & Tropical Medicine Keppel Street London WC1E 7HT United Kingdom

Type

Article

Source Title

Nature Communications

ISSN

20411723

Year

2023

Volume

14

Issue

1

Open Access

All Open Access Gold Green

Publisher

Nature Research

DOI

10.1038/s41467-023-36282-w

Abstract

The genetics underlying tuberculosis (TB) pathophysiology are poorly understood. Human genome-wide association studies have failed so far to reveal reproducible susceptibility loci attributed in part to the influence of the underlying Mycobacterium tuberculosis (Mtb) bacterial genotype on the outcome of the infection. Several studies have found associations of human genetic polymorphisms with Mtb phylo-lineages but studies analysing genome-genome interactions are needed. By implementing a phylogenetic tree-based Mtb-to-human analysis for 714 TB patients from Thailand we identify eight putative genetic interaction points (P < 5 ? 10?8) including human loci DAP and RIMS3 both linked to the IFN? cytokine and host immune system as well as FSTL5 previously associated with susceptibility to TB. Many of the corresponding Mtb markers are lineage specific. The genome-to-genome analysis reveals a complex interactome picture supports host-pathogen adaptation and co-evolution in TB and has potential applications to large-scale studies across many TB endemic populations matched for host-pathogen genomic diversity. ? 2023 The Author(s).

Industrial Classification

Health Care and Social Assistance

License

CC BY

Rights

Authors

Publication Source

WOS

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