Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese.
case_control · Level III
Where this comes from
- Record sourced from PubMed, PMID 30287856.
- Also identified by DOI 10.1038/s41467-018-06539-w and PMC identifier 6172286.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), and remains a leading public health problem. Previous studies have identified host genetic factors that contribute to Mtb infection outcomes. However, much of the heritability in TB remains unaccounted for and additional susceptibility loci most likely exist. We perform a multistage genome-wide association study on 2949 pulmonary TB patients and 5090 healthy controls (833 cases and 1220 controls were genome-wide genotyped) from Han Chinese population. We discover two risk loci: 14q24.3 (rs12437118, P<sub>combined</sub> = 1.72 × 10<sup>-11</sup>, OR = 1.277, ESRRB) and 20p13 (rs6114027, P<sub>combined</sub> = 2.37 × 10<sup>-11</sup>, OR = 1.339, TGM6). Moreover, we determine that the rs6114027 risk allele is related to decreased TGM6 transcripts in PBMCs from pulmonary TB patients and severer pulmonary TB disease. Furthermore, we find that tgm6-deficient mice are more susceptible to Mtb infection. Our results provide new insights into the genetic etiology of TB.
Medical subject headings
- Receptors, Estrogen
- Transglutaminases
- Tuberculosis