학술논문
Genome-wide host-pathogen analyses reveal genetic interaction points in tuberculosis disease.
Document Type
Academic Journal
Author
Phelan J; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Gomez-Gonzalez PJ; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Andreu N; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Omae Y; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Toyo-Oka L; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Yanai H; Fukujuji Hospital and Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Japan.; Miyahara R; Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, Japan.; Nedsuwan S; Chiangrai Prachanukroh Hospital, Chiangrai, Thailand.; de Sessions PF; Genome Institute of Singapore, One North, Singapore.; Campino S; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Sallah N; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Parkhill J; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.; Smittipat N; National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.; Palittapongarnpim P; National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.; Mushiroda T; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Kubo M; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.; Tokunaga K; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Mahasirimongkol S; Medical Genetics Center, Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand.; Hibberd ML; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. martin.hibberd@lshtm.ac.uk.; Clark TG; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. taane.clark@lshtm.ac.uk.; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom. taane.clark@lshtm.ac.uk.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
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 IFNγ 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).)
(© 2023. The Author(s).)