Estrada, KarolWhelan, Christopher W.Zhao, FengmeiBronson, PaolaHandsaker, RobertSun, ChaoCarulli, John P.Harris, TimRansohoff, Richard M.McCarroll, StevenDay-Williams, Aaron G.Greenberg, Benjamin M.MacArthur, Daniel2018-06-272018Estrada, K., C. W. Whelan, F. Zhao, P. Bronson, R. E. Handsaker, C. Sun, J. P. Carulli, et al. 2018. “A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica.” Nature Communications 9 (1): 1929. doi:10.1038/s41467-018-04332-3. http://dx.doi.org/10.1038/s41467-018-04332-3.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37160123Neuromyelitis 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.en-USJournal Article2018-06-2710.1038/s41467-018-04332-3