jjgilchrist/leprosy_GWAS

Code and source data for GWAS of leprosy in Malawi and Mali # leprosy_GWAS **Genome-wide association study of leprosy in Malawi and Mali.** (PLoS Pathogens, 2022) journals.plos.org Code and source data for GWAS of leprosy in Malawi and Mali. **Dataset** 612 Malawian participants: 284 leprosy cases, 328 controls. 350 Malian participants: 208 leprosy cases, 142 controls. **Abstract** Leprosy is a chronic infection of the skin and peripheral nerves caused by *Mycobacterium leprae*. Despite recent improvements in disease control, leprosy remains an important cause of infectious disability globally. Large-scale genetic association studies in Chinese, Vietnamese and Indian populations have identified over 30 susceptibility loci for leprosy. There is a significant burden of leprosy in Africa, however it is uncertain whether the findings of published genetic association studies are generalizable to African populations. To address this, we conducted a genome-wide association study (GWAS) of leprosy in Malawian and Malian individuals. In that analysis, we replicated four risk loci previously reported in China, Vietnam and India; MHC Class I and II, *LACC1* and *SLC29A3*. We further identified a novel leprosy susceptibility locus at 10q24 (rs2015583; combined p=8.81x10 -9 ; OR=0.51 [95% CI 0.40-0.64]). Using publicly-available data we characterise regulatory activity at this locus, identifying *ACTR1A* as a candidate mediator of leprosy risk. This locus shows evidence of recent positive selection and demonstrates pleiotropy with established risk loci for inflammatory bowel disease and childhood-onset asthma. A shared genetic architecture for leprosy and inflammatory bowel disease has been previously described. We expand on this, strengthening the hypothesis that selection pressure driven by leprosy has shaped the evolution of autoimmune and atopic disease in modern populations. More broadly, our data highlights the importance of defining the genetic architecture of dise …