Prediction of leprosy in the Chinese population based on a weighted genetic risk score

PLoS Negl Trop Dis. 2018 Sep 19;12(9):e0006789. doi: 10.1371/journal.pntd.0006789. eCollection 2018 Sep.

Abstract

Genome wide association studies (GWASs) have revealed multiple genetic variants associated with leprosy in the Chinese population. The aim of our study was to utilize the genetic variants to construct a risk prediction model through a weighted genetic risk score (GRS) in a Chinese set and to further assess the performance of the model in identifying higher-risk contact individuals in an independent set. The highest prediction accuracy, with an area under the curve (AUC) of 0.743 (95% confidence interval (CI): 0.729-0.757), was achieved with a GRS encompassing 25 GWAS variants in a discovery set that included 2,144 people affected by leprosy and 2,671 controls. Individuals in the high-risk group, based on genetic factors (GRS > 28.06), have a 24.65 higher odds ratio (OR) for developing leprosy relative to those in the low-risk group (GRS≤18.17). The model was then applied to a validation set consisting of 1,385 people affected by leprosy and 7,541 individuals in contact with leprosy, which yielded a discriminatory ability with an AUC of 0.707 (95% CI: 0.691-0.723). When a GRS cut-off value of 22.38 was selected with the optimal sensitivity and specificity, it was found that 39.31% of high risk contact individuals should be screened in order to detect leprosy in 64.9% of those people affected by leprosy. In summary, we developed and validated a risk model for the prediction of leprosy that showed good discrimination capabilities, which may help physicians in the identification of patients coming into contact with leprosy and are at a higher-risk of developing this condition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing / methods*
  • Humans
  • Leprosy / genetics*
  • Male
  • Middle Aged
  • Models, Genetic
  • Risk Assessment
  • Young Adult

Grants and funding

This work was funded by grants from the National Key Research and Development Program of China (2016YFE0201500), the Natural Science Foundation of Shandong Province (JQ201616), the Innovation Project of Shandong Academy of Medical Sciences, the National Clinical Key Project of Dermatology and Venereology, the Shandong Provincial Advanced Taishan Scholar Construction Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.