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

Autor: Estrada K; Translational Genome Sciences, Biogen, Cambridge, MA, 02142, USA., Whelan CW; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA., Zhao F; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA., Bronson P; Translational Genome Sciences, Biogen, Cambridge, MA, 02142, USA., Handsaker RE; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA., Sun C; Translational Genome Sciences, Biogen, Cambridge, MA, 02142, USA., Carulli JP; Translational Genome Sciences, Biogen, Cambridge, MA, 02142, USA., Harris T; Translational Genome Sciences, Biogen, Cambridge, MA, 02142, USA.; Bioverativ, Waltham, MA, 02451, USA., Ransohoff RM; Neuroimmunology, Acute Neurology and Pain, Biogen, Cambridge, MA, 02142, USA.; Third Rock Ventures, Boston, MA, 02116, USA., McCarroll SA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.; Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA., Day-Williams AG; Translational Genome Sciences, Biogen, Cambridge, MA, 02142, USA.; Genetics and Pharmacogenomics, Merck, Boston, MA, 02115, USA., Greenberg BM; Department of Neurology and Neurotherapeutics, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. Benjamin.greenberg@utsouthwestern.edu., MacArthur DG; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. danmac@broadinstitute.org.; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA. danmac@broadinstitute.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 May 16; Vol. 9 (1), pp. 1929. Date of Electronic Publication: 2018 May 16.
DOI: 10.1038/s41467-018-04332-3
Abstrakt: 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.
Databáze: MEDLINE