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

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

来源：Nature Communications, 2018, 9(1): 1929.

DOI：10.1038/s41467-018-04332-3

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.

• 出版日期2018-5-16
• 单位MIT