Evaluate the host genetic effects of tuberculosis-associated variants on diabetes Open Access

Abstract

Evaluate the host genetic effects of tuberculosis-associated variants on diabetes 

Abstract 

Background: 

Numerous host genetic variants have been linked to tuberculosis (TB) from the genetic association studies. Comorbidities between TB and non-communicable diseases, such as diabetes, have been an increasing health burden. However, the molecular and genetic mechanism linking TB and diabetes hasn’t been explored. 

Methods: 

We performed an association study to evaluate the effects of seven TB-related host genetic variants on type II diabetes (T2DM) using the genetic and phenotypic data from the UK Biobank. 409,692 participants of European ancestry including 13,976 T2DM cases and 2,177 T1DM cases defined by ICD-10 diagnosis codes. 

Results: 

One out of seven SNPs were significantly associated with T2DM adjusted for age, sex, BMI, smoke, alcohol use and population structure after correction for multiple testing. The C allele of SNP rs3135359 (BTNL2 gene on HLA-A) is associated with increased risk for TB infection (OR 1.21 95% CI 1.18-1.24), increased risk for T2DM (OR 1.06 95% CI 1.025-1.096), and increased risk for T1DM (OR 1.72 95% CI 1.57-1.88 ). The rs3135359 is strongly associated with thyroid disease and additional autoimmune diseases including multiple sclerosis and rheumatoid arthritis. 

Conclusion: 

Our findings support that the host genetic effects may partially explain observed disease comorbidities between TB susceptibility and T2DM. Our analyses demonstrated common genetic factors underlying chronic infection and non-communicable disease, particularly via immune functions. 

Table of Contents

 Table of Contents 

1. Distribution Agreement 

2. Approval Sheet 

3. Abstract Cover Page 

4. Abstract 

5. Cover Page 

6. Acknowledgments 

7. Table of Contents (including a list of tables and figures, optional) 

8. Chapter I: Background/Literature Review 

9. Chapter II: Manuscript (peer-reviewed journal article style) 

a. The title, Author(s), Abstract 

b. Introduction 

c. Methods 

d. Results 

e. Discussion 

i. Strengths and limitations 

f. References 

g. Tables 

h. Figures/Figure Legends 

10. Chapter III: Summary, Public Health Implications, Possible Future Directions 

11. Appendices 

About this Master's Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Global Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Biology, Genetics Health Sciences, Epidemiology Biology, Molecular
Keyword	Host genetic effect Variants SNPs Diabetes TB UK Biobank
Committee Chair / Thesis Advisor	Yan Sun, Emory University

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