A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica

Karol Estrada, Christopher W. Whelan, Fengmei Zhao, Paola Bronson, Robert E. Handsaker, Chao Sun, John P. Carulli, Tim Harris, Richard M. Ransohoff, Steven A. McCarroll, Aaron G. Day-Williams, Benjamin M. Greenberg, Daniel G. MacArthur

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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.

Original languageEnglish (US)
Article number1929
JournalNature communications
Issue number1
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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