Catherine M Stein1,2, Lindsay Sausville1, Christian Wejse3, Rafal S Sobota4, Nicola M Zetola5,6,7, Philip C Hill8, W Henry Boom2, William K Scott9, Giorgio Sirugo10, Scott M Williams1. 1. Department of Population and Quantitative Health Sciences, Cleveland, OH. 2. Tuberculosis Research Unit, Case Western Reserve University, Cleveland, OH. 3. Dept of Infectious Diseases/Center for Global Health, Aarhus University, Aarhus, Denmark. 4. The Ken and Ruth Davee Department of Neurology, Northwestern University, Chicago, IL. 5. Division of Infectious Diseases, University of Pennsylvania, Philadelphia, PA 19104, USA. 6. Botswana-UPenn Partnership, Gaborone, Botswana. 7. Department of Medicine, University of Botswana, Gaborone, Botswana. 8. Centre for International Health, University of Otago, Dunedin, New Zealand. 9. Department of Human Genetics and Genomics, University of Miami School of Medicine, Miami, FL. 10. Institute for Translational Medicine and Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Abstract
PURPOSE OF REVIEW: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a major public health threat globally. Several lines of evidence support a role for host genetic factors in resistance/susceptibility to TB disease and MTB infection. However, results across candidate gene and genome-wide association studies (GWAS) are largely inconsistent, so a cohesive genetic model underlying TB risk has not emerged. RECENT FINDINGS: Despite the difficulties in identifying consistent genetic associations, genetic studies of TB and MTB infection have revealed a few well-documented loci. These well validated genes are presented in this review, but there remains a large gap in how these genes translate into better understanding of TB. To address this, we present a pathway based extension of standard association analyses, seeding the results with the best validated genes from candidate gene and GWAS studies. SUMMARY: Several pathways were significantly enriched using pathway analyses that may help to explain population patterns of TB risk. In conclusion, we advocate for novel approaches to the study of host genetic analysis of TB that extend traditional association approaches.
PURPOSE OF REVIEW: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a major public health threat globally. Several lines of evidence support a role for host genetic factors in resistance/susceptibility to TB disease and MTB infection. However, results across candidate gene and genome-wide association studies (GWAS) are largely inconsistent, so a cohesive genetic model underlying TB risk has not emerged. RECENT FINDINGS: Despite the difficulties in identifying consistent genetic associations, genetic studies of TB and MTB infection have revealed a few well-documented loci. These well validated genes are presented in this review, but there remains a large gap in how these genes translate into better understanding of TB. To address this, we present a pathway based extension of standard association analyses, seeding the results with the best validated genes from candidate gene and GWAS studies. SUMMARY: Several pathways were significantly enriched using pathway analyses that may help to explain population patterns of TB risk. In conclusion, we advocate for novel approaches to the study of host genetic analysis of TB that extend traditional association approaches.
Entities:
Keywords:
Tuberculosis genetics; Tuberculosis pathways and disease; Tuberculosis resistance
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