Marlo Möller1, Craig J Kinnear. 1. DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Abstract
PURPOSE OF REVIEW: Multiple lines of evidence support a role of the host genetic component in Mycobacterium tuberculosis infection and disease progression. However, genomic studies of tuberculosis susceptibility have been disappointing compared with that of other complex disorders. Recently the field has explored alternative strategies to facilitate locus discovery. Results emanating from these efforts during the last 18 months are addressed in this review. RECENT FINDINGS: There has been a renewed focus on the refinement of phenotypic definitions of infection and disease as well as on age-related, sex-specific and population-specific effects. Genome-wide association studies have yielded candidate genes but the findings have not always been transferable to all population groups. Candidate gene association studies remain popular as it is used for GWAS replication and is affordable, particularly in lower and middle-income countries. Pharmacogenetic studies involving tuberculosis drugs may locate variants that can be cost-effectively genotyped to identify individuals at risk of developing adverse events during treatment. SUMMARY: Additional GWAS and candidate gene association studies of crudely defined study participants are unlikely to make further important contributions to the TB susceptibility field. Instead refined phenotyping will allow the elucidation of genetic mechanisms contributing to infection and disease in distinct populations and the calculation of polygenic risk scores.
PURPOSE OF REVIEW: Multiple lines of evidence support a role of the host genetic component in Mycobacterium tuberculosis infection and disease progression. However, genomic studies of tuberculosis susceptibility have been disappointing compared with that of other complex disorders. Recently the field has explored alternative strategies to facilitate locus discovery. Results emanating from these efforts during the last 18 months are addressed in this review. RECENT FINDINGS: There has been a renewed focus on the refinement of phenotypic definitions of infection and disease as well as on age-related, sex-specific and population-specific effects. Genome-wide association studies have yielded candidate genes but the findings have not always been transferable to all population groups. Candidate gene association studies remain popular as it is used for GWAS replication and is affordable, particularly in lower and middle-income countries. Pharmacogenetic studies involving tuberculosis drugs may locate variants that can be cost-effectively genotyped to identify individuals at risk of developing adverse events during treatment. SUMMARY: Additional GWAS and candidate gene association studies of crudely defined study participants are unlikely to make further important contributions to the TB susceptibility field. Instead refined phenotyping will allow the elucidation of genetic mechanisms contributing to infection and disease in distinct populations and the calculation of polygenic risk scores.
Authors: Haiko Schurz; Brigitte Glanzmann; Nicholas Bowker; Ronald van Toorn; Regan Solomons; Johan Schoeman; Paul D van Helden; Craig J Kinnear; Eileen G Hoal; Marlo Möller Journal: Front Neurol Date: 2022-03-25 Impact factor: 4.003