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To date, genome‐wide association studies (GWASs) have discovered 35 susceptible loci of leprosy; however, the cumulative effects of these loci can only partially explain the overall risk of leprosy, and the causal variants and genes within these loci remain unknown. Here, we conducted out new GWASs in two independent cohorts of 5007 cases and 4579 controls and then a meta‐analysis in these newly generated and multiple previously published (2277 cases and 3159 controls) datasets were performed. Three novel and 15 previously reported risk loci were identified from these datasets, increasing the known leprosy risk loci of explained genetic heritability from 23.0 to 38.5%. A comprehensive fine‐mapping analysis was conducted, and 19 causal variants and 14 causal genes were identified. Specifically, manual checking of epigenomic information from the Epimap database revealed that the causal variants were mainly located within the immune‐relevant or immune‐specific regulatory elements. Furthermore, by using gene‐set, tissue, and cell‐type enrichment analyses, we highlighted the key roles of immune‐related tissues and cells and implicated the PD‐1 signaling pathways in the pathogenetic mechanism of leprosy. Collectively, our study identified candidate causal variants and elucidated the potential regulatory and coding mechanisms for genes associated with leprosy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article discusses two cases of fever, rash, and organ involvement during the treatment of leprosy. The first patient, a 65-year-old man, developed a high fever and a generalized rash after 27 days of treatment. The second patient, a 39-year-old woman, developed a fever and a pruritic rash 21 days after treatment. The symptoms in both cases were initially suspected to be a drug-induced hypersensitivity syndrome (DIHS) caused by the medication dapsone (DDS). The diagnosis of DDS-induced hypersensitivity syndrome was confirmed through an HLA-B*13:01 test. Treatment with corticosteroids led to improvement in both patients. The article emphasizes the importance of timely diagnosis and differential diagnosis in the treatment of leprosy and highlights the value of the HLA-B*13:01 test in preventing DDS syndrome. [Extracted from the article]

The article focuses on the Genome-Wide Association Study of single nucleotide polymorphisms (SNP) of association of PARK2 and PACRG with leprosy in Chinese population. The study found no remarkable association of Chinese population with the risk SNPs within the PARK2 and PACRG leprosy region. It is noted that there may be a suggestive association of SNPs with ethnic heterogeneity of susceptibility to leprosy.

Of eight leprosy susceptibility loci identified by genome-wide association studies, five have been implicated in Crohn disease, suggesting a common genetic fingerprint between leprosy and inflammatory bowel disease (IBD). Here, we conducted a multiple-stage genetic association study of 133 IBD susceptibility loci in multiple leprosy samples (totaling 4,971 leprosy cases and 5,503 controls) from a Chinese population and discovered two associations at rs2058660 on 2q12.1 (p = 4.57 × 10−19; odds ratio [OR] = 1.30) and rs6871626 on 5q33.3 (p = 3.95 × 10−18; OR = 0.75), implicating IL18RAP/IL18R1 and IL12B as susceptibility genes for leprosy. Our study reveals the important role of IL12/IL18-mediated transcriptional regulation of IFN-γ production in leprosy, and together with previous findings, it demonstrates the shared genetic susceptibility between infectious and inflammatory diseases. [Copyright &y& Elsevier]