Genome-wide association study of leprosy in Malawi and Mali.
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...
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Public Library of Science (PLoS)
2022-09-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010312&type=printable |
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| author | James J Gilchrist Kathryn Auckland Tom Parks Alexander J Mentzer Lily Goldblatt Vivek Naranbhai Gavin Band Kirk A Rockett Ousmane B Toure Salimata Konate Sibiri Sissoko Abdoulaye A Djimdé Mahamadou A Thera Ogobara K Doumbo Samba Sow Sian Floyd Jörg M Pönnighaus David K Warndorff Amelia C Crampin Paul E M Fine Benjamin P Fairfax Adrian V S Hill |
| author_facet | James J Gilchrist Kathryn Auckland Tom Parks Alexander J Mentzer Lily Goldblatt Vivek Naranbhai Gavin Band Kirk A Rockett Ousmane B Toure Salimata Konate Sibiri Sissoko Abdoulaye A Djimdé Mahamadou A Thera Ogobara K Doumbo Samba Sow Sian Floyd Jörg M Pönnighaus David K Warndorff Amelia C Crampin Paul E M Fine Benjamin P Fairfax Adrian V S Hill |
| author_sort | James J Gilchrist |
| collection | DOAJ |
| description | 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 (327 cases, 436 controls) and Malian (247 cases, 368 controls) 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 = 8.81 × 10-9; 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 disease across genetically diverse populations, and that disease insights derived from GWAS in one population may not translate to all affected populations. |
| format | Article |
| id | doaj-art-1b686b47b5c44125a70cea80ed468575 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2022-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-1b686b47b5c44125a70cea80ed4685752025-08-20T02:22:26ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742022-09-01189e101031210.1371/journal.ppat.1010312Genome-wide association study of leprosy in Malawi and Mali.James J GilchristKathryn AucklandTom ParksAlexander J MentzerLily GoldblattVivek NaranbhaiGavin BandKirk A RockettOusmane B ToureSalimata KonateSibiri SissokoAbdoulaye A DjimdéMahamadou A TheraOgobara K DoumboSamba SowSian FloydJörg M PönnighausDavid K WarndorffAmelia C CrampinPaul E M FineBenjamin P FairfaxAdrian V S HillLeprosy 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 (327 cases, 436 controls) and Malian (247 cases, 368 controls) 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 = 8.81 × 10-9; 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 disease across genetically diverse populations, and that disease insights derived from GWAS in one population may not translate to all affected populations.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010312&type=printable |
| spellingShingle | James J Gilchrist Kathryn Auckland Tom Parks Alexander J Mentzer Lily Goldblatt Vivek Naranbhai Gavin Band Kirk A Rockett Ousmane B Toure Salimata Konate Sibiri Sissoko Abdoulaye A Djimdé Mahamadou A Thera Ogobara K Doumbo Samba Sow Sian Floyd Jörg M Pönnighaus David K Warndorff Amelia C Crampin Paul E M Fine Benjamin P Fairfax Adrian V S Hill Genome-wide association study of leprosy in Malawi and Mali. PLoS Pathogens |
| title | Genome-wide association study of leprosy in Malawi and Mali. |
| title_full | Genome-wide association study of leprosy in Malawi and Mali. |
| title_fullStr | Genome-wide association study of leprosy in Malawi and Mali. |
| title_full_unstemmed | Genome-wide association study of leprosy in Malawi and Mali. |
| title_short | Genome-wide association study of leprosy in Malawi and Mali. |
| title_sort | genome wide association study of leprosy in malawi and mali |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1010312&type=printable |
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