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

Nature Communications
Karol EstradaDaniel G MacArthur

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.

References

Oct 9, 2002·Journal of Molecular Biology·Jean M H van den ElsenDavid E Isenman
May 24, 2006·Neurology·D M WingerchukB G Weinshenker
Nov 25, 2006·Disease Markers·Brian G WeinshenkerVanda A Lennon
Mar 21, 2009·Multiple Sclerosis : Clinical and Laboratory Research·H ZéphirJ de Seze
Oct 24, 2009·Neurobiology of Disease·Ho Jin KimHyoung Doo Shin
Dec 10, 2009·Multiple Sclerosis : Clinical and Laboratory Research·Doralina Guimaraães BrumEduardo Antonio Donadi
Jul 10, 2010·Bioinformatics·Cristen J WillerGonçalo R Abecasis
Feb 15, 2011·Nature Genetics·Robert E HandsakerSteven A McCarroll
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Richard M Ransohoff
May 23, 2012·Lancet Neurology·Marios C Papadopoulos, A S Verkman
May 8, 2013·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Michele T PatoCarlos N Pato
Jun 14, 2013·PloS One·Xiaoming JiaPaul I W de Bakker
Oct 1, 2013·Nature Genetics·UNKNOWN International Multiple Sclerosis Genetics Consortium (IMSGC)Jacob L McCauley
Mar 19, 2014·Molecular Immunology·Balthasar A HeestersMichael C Carroll
May 17, 2014·Seminars in Immunopathology·Markus Krumbholz, Edgar Meinl
Jul 17, 2014·Bioinformatics·Ezequiel L NicolazziJohn L Williams
Aug 12, 2014·Journal of Neuroimmunology·Petra NytrovaMarten Trendelenburg
Jan 27, 2015·Nature Genetics·Robert E HandsakerSteven A McCarroll
Jan 11, 2016·American Journal of Human Genetics·Brian L Browning, Sharon R Browning
Jan 28, 2016·Nature·Aswin SekarSteven A McCarroll
Oct 28, 2016·Nature Genetics·Po-Ru LohAlkes L Price

❮ Previous
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Citations

Jul 30, 2019·Neuropathology and Applied Neurobiology·V T W Chang, H-M Chang
Jul 11, 2019·Brain : a Journal of Neurology·Kathryn C FitzgeraldPeter A Calabresi
Sep 9, 2020·Current Opinion in Ophthalmology·Kathryn B HolroydMichael Levy
Mar 5, 2020·Auto- Immunity Highlights·Sergio Muñiz-CastrilloJérôme Honnorat
Mar 16, 2019·Clinical Medicine : Journal of the Royal College of Physicians of London·Saif HudaAnu Jacob
Dec 12, 2019·Frontiers in Veterinary Science·Christoforos PosporisAnnette Wessmann
Mar 22, 2020·Neurology. Neuroimmunology and Neuroinflammation·Arlette L BruijstensBeatrijs H A Wokke
Sep 27, 2020·Annals of Clinical and Translational Neurology·Takuya MatsushitaUNKNOWN Japan Multiple Sclerosis Genetic Consortium
Jun 6, 2020·Nature·Nolan KamitakiSteven A McCarroll
May 16, 2019·Arquivos de neuro-psiquiatria·Cláudia Suemi Kamoi KayLineu Cesar Werneck
Jan 10, 2021·Scientific Reports·Marcos Papais AlvarengaRegina Maria Papais-Alvarenga
Oct 24, 2020·Nature Reviews. Disease Primers·Sven JariusBrigitte Wildemann
Nov 6, 2020·Neurology. Neuroimmunology and Neuroinflammation·Lekha PanditTanuja Chitnis
Feb 10, 2021·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Xiaonan ZhongWei Qiu
Oct 4, 2020·Current Opinion in Ophthalmology·Kathryn B HolroydMichael Levy
Oct 17, 2020·Journal of Clinical Apheresis·Tina S IpeJay S Raval
Dec 2, 2020·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Chunping CuiWei Qiu
May 13, 2021·Nature Reviews. Immunology·Harald Prüss
May 19, 2021·BMC Bioinformatics·Emily A KingJacob F Degner
Aug 14, 2021·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·M A Sherman, A N Boyko

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Methods Mentioned

BETA
genotyping
enzyme-linked immunosorbent assay
flow cytometry
PCR

Software Mentioned

GATK
VQSR
Affymetrix Power Tools
HaplotypeCaller
METAL
GenomeSTRiP
Sample MR
InPSYght
Plink
SNP2HLA

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