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

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.

SUBMITTER: Estrada K

PROVIDER: S-EPMC5955905 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Estrada Karol K Whelan Christopher W CW Zhao Fengmei F Bronson Paola P Handsaker Robert E RE Sun Chao C Carulli John P JP Harris Tim T Ransohoff Richard M RM McCarroll Steven A SA Day-Williams Aaron G AG Greenberg Benjamin M BM MacArthur Daniel G DG

Nature communications 20180516 1

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 maj ...[more]

PMID: 29769526

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Project description:Background and purposeConventional MR imaging typically yields normal images of the brain or indicates lesions in areas of high aquaporin expression in patients with neuromyelitis optica. Diffusional kurtosis imaging was applied in patients with neuromyelitis optica to determine whether this technique could detect alterations in diffusion and diffusional kurtosis parameters in normal-appearing white matter and to explore the relationship between diffusional kurtosis imaging and DTI parameters.Materials and methodsThirteen patients with neuromyelitis optica and 13 healthy controls underwent MR imaging of the brain with conventional and diffusional kurtosis imaging sequences. Tract-based spatial statistics and region-of-interest-based analyses were conducted to identify differences between patients with neuromyelitis optica and controls through conventional DTI and diffusional kurtosis imaging parameters. The parameters were correlated to determine the potential relationship between them.ResultsCompared with healthy controls, several diffusional kurtosis imaging and DTI parameters were altered in various fiber tracts of patients with neuromyelitis optica (P < .05). A significant decrease (P < .05) in radial kurtosis was observed in the corpus callosum and anterior corona radiata and left optic radiation. Differences (P < .1) in mean kurtosis were found in patients with neuromyelitis optica. We found a negative correlation between diffusional kurtosis imaging (radial kurtosis, axial kurtosis, mean kurtosis) and the corresponding DTI parameters (radial diffusivity, axial diffusivity, mean diffusivity). Positive correlations were found for radial kurtosis and mean kurtosis with fractional anisotropy.ConclusionsThis study demonstrated differences in conventional diffusion and diffusional kurtosis parameters, especially radial kurtosis, in the normal-appearing white matter of patients with neuromyelitis optica compared with healthy controls. Larger studies of patients with neuromyelitis optica should be performed to assess the potential clinical impact of these findings.

Dataset Information

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

Publications

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

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