We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica.
- Authors
Estrada, Karol; Whelan, Christopher W.; Fengmei Zhao; Bronson, Paola; Handsaker, Robert E.; Chao Sun; Carulli, John P.; Harris, Tim; Ransohoff, Richard M.; McCarroll, Steven A.; Day-Williams, Aaron G.; Greenberg, Benjamin M.; MacArthur, Daniel G.
- Abstract
Neuromyelitis optica (NMO) is a rare autoimmune disease that affects the optic nerve and spinal cord. Most NMO patients ( > 70%) are seropositive for circulating autoantibodies against aquaporin 4 (NMO-IgG+). Here, we meta-analyze whole-genome sequences from 86 NMO cases and 460 controls with genome-wide SNP array from 129 NMO cases and 784 controls to test for association with SNPs and copy number variation (total N = 215 NMO cases, 1244 controls). We identify two independent signals in the major histocompatibility complex (MHC) region associated with NMO-IgG+, one of which may be explained by structural variation in the complement component 4 genes. Mendelian Randomization analysis reveals a significant causal effect of known systemic lupus erythematosus (SLE), but not multiple sclerosis (MS), risk variants in NMO-IgG+. Our results suggest that genetic variants in the MHC region contribute to the etiology of NMO-IgG+ and that NMO-IgG+ is genetically more similar to SLE than MS.
- Subjects
NEUROMYELITIS optica; SYSTEMIC lupus erythematosus; MAJOR histocompatibility complex; SPINAL nerves; OPTIC nerve; SPINAL cord; NATALIZUMAB
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-04332-3