An infectious disease caused by Mycobacterium leprae, curable with multidrug therapy, whose genetics keep pointing at the same immune pathways this site already covers for Crohn's disease, ulcerative colitis and psoriasis.
Leprosy (Hansen's disease) is caused by Mycobacterium leprae, a bacterium that cannot be grown in laboratory culture, which has long made it a harder disease to study than most. It remains a public health concern in parts of Asia, Africa and Latin America — India alone reports the largest share of new cases worldwide each year — even though it has been reliably curable with multidrug therapy since the 1980s. Only a minority of people exposed to M. leprae ever develop the disease, which is the first clue that host genetics plays a real role.
Zhang et al. 2009, in the New England Journal of Medicine, ran the first genome-wide scan for leprosy: 706 cases and 1,225 controls in discovery, replicated across three further sample sets totalling 3,254 cases and 5,955 controls. It found the HLA-DR-DQ region and RIPK2, and — notably — statistical evidence that NOD2 and RIPK2 interact, which lines up with known biology: the two proteins physically partner in a complex that lets innate immune cells sense bacterial peptidoglycan.
Zhang et al. 2011 found two more loci in an expanded version of the same cohort: rs2275606 in RAB32 (OR=1.30, increasing risk) and rs3762318 in IL23R (OR=0.69, i.e. protective). Liu et al. 2015 scaled the search up to 8,313 cases and 16,017 controls, confirmed every previously published locus, and found six new ones — gene-prioritisation analysis pointed to BATF3, CCDC88B and CIITA-SOCS1 — while also finding that leprosy susceptibility loci overlap substantially with loci for other immune diseases. Wang et al. 2016, in a similarly large cohort (8,156 cases, 15,610 controls), found four further loci including rs6807915 near SYN2, noting that 18 loci were already established for leprosy by that point.
All four studies were conducted in Chinese populations — a real limitation worth stating plainly, since leprosy's global burden today sits mostly in South Asia, Africa and Latin America, and whether these specific loci generalise to those populations is not something these studies can answer on their own.
IL23R is not new to this site. A different IL23R variant already sits on this site's Crohn's disease, ulcerative colitis and psoriasis pages. That is not a coincidence of gene naming — interleukin-23/Th17 immune signalling is a genuinely shared pathway across leprosy susceptibility and several autoimmune diseases, replicated independently in study after study.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 2 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Jung S et al. 2022, Human molecular genetics rs9271011 (near HLA-DRB1) — PMID:35512355
Gzara C et al. 2020, PLoS pathogens rs114598080 (HLA-C) — PMID:32421744
Leprosy is diagnosed clinically (skin lesions, nerve involvement) and confirmed with skin smears or biopsy, not by genotype. It is curable with multidrug therapy (a combination of antibiotics, standard since the 1980s), and untreated disease is what leads to the peripheral nerve damage and disability historically associated with it. None of that is decided by the variants on this page.
The real value of these findings is mechanistic rather than diagnostic: they show, with unusual clarity for an infectious disease, that a specific innate-immune sensing pathway (NOD2-RIPK2) and a specific adaptive-immune signalling pathway (IL-23/Th17) both genuinely affect who develops disease after exposure to the same bacterium. That is a research contribution to understanding infection susceptibility broadly, not a personal risk calculator — most people carrying a "risk" allele at any one of these loci will never encounter M. leprae at all, let alone develop leprosy from it.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Leprosy comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 12 of 14 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Leprosy. MyGeneLog™. https://www.mygenelog.com/conditions/leprosy
No. Leprosy is diagnosed clinically and confirmed with skin smears or biopsy. These variants come from genome-wide association studies and are not used diagnostically — most people carrying a risk allele will never be exposed to Mycobacterium leprae at all.
Yes — it has been reliably curable with multidrug therapy since the 1980s. The nerve damage and disability historically associated with leprosy come from untreated disease, not from the infection itself being incurable.
Interleukin-23/Th17 immune signalling is a genuinely shared pathway across leprosy susceptibility and several autoimmune diseases, replicated independently across different studies of each condition — not a coincidence of gene naming.
Not established. All four studies behind this page were conducted in Chinese cohorts, and whether these specific loci hold in the South Asian, African and Latin American populations where leprosy's burden is now concentrated is an open question.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.