DNA Code Unraveled for Rare Neurologic Disease

Neuromyelitis optica (NMO) is a potentially fatal disease in which the immune system attacks cells in the optic nerve and spinal cord, leaving some patients blind and/or paralyzed.

Patients can recover most of their function through medications and physical rehabilitation, though many are misdiagnosed with multiple sclerosis and face a higher risk of relapse and permanent damage due to lack of proper therapy.


A team of scientists from various institution and led by those at the Broad Institute (Cambridge, MA, USA) used genetic data from more than 1,200 participants which may help scientists improve treatments of neuromyelitis optica (NMO). The team meta-analyzed whole-genome sequences from 86 NMO cases and 460 controls with genome-wide single nucleotide polymorphism (SNP) array from 129 NMO cases and 784 controls to test for association with SNPs and copy number variation (total 215 NMO cases, 1,244 controls).

The investigators determined anti-aquaporin 4 (AQP4) serostatus via standardized assays, including enzyme-linked immunosorbent assay (ELISA) or cell-based assay (CBA). ELISA-based detection was obtained from one of the numerous laboratories that offer the test. CBAs were obtained from the Mayo Clinic Laboratories (Rochester, MN, USA). The team also obtained DNA from 144 NMO cases (78 NMO-immunoglobulin G (IgG)+ / 68 NMO-IgG−). Sequence reads were processed and aligned to a reference genome. Other techniques were used to support the study.

The team identified 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 four genes. Mendelian Randomization analysis revealed a significant causal effect of known systemic lupus erythematosus (SLE), but not multiple sclerosis (MS), risk variants in NMO-IgG+.

Benjamin Greenberg, MD, a neurologist and a senior author of the study, said, “This outcome shows that doing in-depth studies pays off, and more studies like this may be needed to find the problem behind other rare conditions. By taking a rare disease and doing more than just reading every third or fourth page of genetic code, we have modeled NMO in a much more accurate way.” The study was published on May 16, 2018, in the journal Nature Communications.

Related Links:
Broad Institute
Mayo Clinic Laboratories