Identification of genetic risk loci associated with aquaporin 4-positive NMOSD: a genome-wide association study
Journal: The Lancet Neurology; May 1, 2026
Author(s): Kathrine E Attfield, Angelos P Armen, Subita Balaram Kuttikkatte, Redwan Farooq, Anna G Francis, Calliope A Dendrou, M Isabel Leite, Patrick Waters; International NMOSD Genetics Consortium; Brian G Weinshenker, Konrad J Karczewski, Benjamin M Neale, Lise Torp Jensen, Jamie Rossjohn, Ralf Gold, Thomas Korn, Gil McVean, Jacqueline Palace, Lars Fugger
Why do people develop NMOSD? A large-scale study to understand possible genetic factors
This was a large-scale study aiming to identify why some people develop NMOSD and if there may be any common genetic patterns among NMOSD patients and between patients with NMOSD and those with other autoimmune disease.
The study involved the genetic data of 2833 people, including 1573 with aquaporin4 (AQP4) antibody-positive NMOSD and 1260 people who were a mix of individuals without NMOSD but either related to the patients, or unrelated healthy individuals, or patients with other autoimmune diseases. A genome-wide association study (GWAS) was conducted, which means that many small genetic differences among all the people involved in the study were carefully assessed to identify similarities, differences, and patterns. DNA samples used for the study came from hospitals and research centers all over the world, through the International NMOSD Genetics Consortium.
A secondary GWAS was conducted with all the samples that had European ancestry—a total of 1857 samples, including 803 with AQP4-positive NMOSD and 1054 controls.
Three main genetic features were found that might be associated with a greater risk of NMOSD:
- A genetic pattern related to lower levels of a protein called C4, which plays an important role in removing potentially harmful immune cells in the immune system.
- A variation in HLA genes, which help the immune system tell the body’s own cells from foreign threats like viruses and bacteria.
- Variations in elements of the TYK2–STAT4 pathway, which is a communication channel within the immune system. Autoimmune diseases can arise when the TYK2–STAT4 pathway does not function properly.
This was the largest genetic study of AQP4-positive NMOSD so far. Understanding genetic patterns can help the potential cause to be identified and treatments to be developed.
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