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A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica
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 gen...
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| Published in: | Nature communications 2018-05, Vol.9 (1), p.1929-10, Article 1929 |
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| creator | 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. |
| description | 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.
Neuromyelitis optica (NMO) is a rare autoimmune condition characterized by inflammation and demyelination of the optic nerve and the spinal cord. Here, Estrada et al. identify NMO susceptibility variants in the MHC region and find that autoantibody-positive NMO genetically overlaps with lupus. |
| doi_str_mv | 10.1038/s41467-018-04332-3 |
| format | article |
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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.
Neuromyelitis optica (NMO) is a rare autoimmune condition characterized by inflammation and demyelination of the optic nerve and the spinal cord. Here, Estrada et al. identify NMO susceptibility variants in the MHC region and find that autoantibody-positive NMO genetically overlaps with lupus.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/s41467-018-04332-3</identifier><identifier>PMID: 29769526</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/23 ; 631/208/205/2138 ; 631/250/371 ; 692/699/249/1313 ; 692/699/375/1411 ; Adult ; Aquaporin 4 ; Aquaporin 4 - immunology ; Autoantibodies ; Autoimmune diseases ; Chronic conditions ; Copy number ; DNA Copy Number Variations ; Etiology ; Female ; Gene sequencing ; Genetic diversity ; Genetic Predisposition to Disease - genetics ; Genetic variance ; Genomes ; Haplotypes ; Humanities and Social Sciences ; Humans ; Immunoglobulin G ; Immunoglobulin G - immunology ; Major histocompatibility complex ; Major Histocompatibility Complex - genetics ; Male ; Middle Aged ; multidisciplinary ; Multiple sclerosis ; Neuromyelitis ; Neuromyelitis Optica - genetics ; Neuromyelitis Optica - immunology ; Nucleotide sequence ; Optic nerve ; Polymorphism, Single Nucleotide ; Risk analysis ; Risk Factors ; Science ; Science (multidisciplinary) ; Single-nucleotide polymorphism ; Spinal cord ; Systemic lupus erythematosus ; Whole Genome Sequencing - methods</subject><ispartof>Nature communications, 2018-05, Vol.9 (1), p.1929-10, Article 1929</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c606t-ae0beb33f718a21d344d1d9c816ac43b12ab190cb460e1efc91939140ca1786a3</citedby><cites>FETCH-LOGICAL-c606t-ae0beb33f718a21d344d1d9c816ac43b12ab190cb460e1efc91939140ca1786a3</cites><orcidid>0000-0002-3128-3547 ; 0000-0003-0175-6910 ; 0000-0001-8446-8468</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2039832485/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2039832485?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29769526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Estrada, Karol</creatorcontrib><creatorcontrib>Whelan, Christopher W.</creatorcontrib><creatorcontrib>Zhao, Fengmei</creatorcontrib><creatorcontrib>Bronson, Paola</creatorcontrib><creatorcontrib>Handsaker, Robert E.</creatorcontrib><creatorcontrib>Sun, Chao</creatorcontrib><creatorcontrib>Carulli, John P.</creatorcontrib><creatorcontrib>Harris, Tim</creatorcontrib><creatorcontrib>Ransohoff, Richard M.</creatorcontrib><creatorcontrib>McCarroll, Steven A.</creatorcontrib><creatorcontrib>Day-Williams, Aaron G.</creatorcontrib><creatorcontrib>Greenberg, Benjamin M.</creatorcontrib><creatorcontrib>MacArthur, Daniel G.</creatorcontrib><title>A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>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.
Neuromyelitis optica (NMO) is a rare autoimmune condition characterized by inflammation and demyelination of the optic nerve and the spinal cord. Here, Estrada et al. identify NMO susceptibility variants in the MHC region and find that autoantibody-positive NMO genetically overlaps with lupus.</description><subject>45</subject><subject>45/23</subject><subject>631/208/205/2138</subject><subject>631/250/371</subject><subject>692/699/249/1313</subject><subject>692/699/375/1411</subject><subject>Adult</subject><subject>Aquaporin 4</subject><subject>Aquaporin 4 - immunology</subject><subject>Autoantibodies</subject><subject>Autoimmune diseases</subject><subject>Chronic conditions</subject><subject>Copy number</subject><subject>DNA Copy Number Variations</subject><subject>Etiology</subject><subject>Female</subject><subject>Gene sequencing</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetic variance</subject><subject>Genomes</subject><subject>Haplotypes</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - immunology</subject><subject>Major histocompatibility complex</subject><subject>Major Histocompatibility Complex - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Multiple sclerosis</subject><subject>Neuromyelitis</subject><subject>Neuromyelitis Optica - genetics</subject><subject>Neuromyelitis Optica - immunology</subject><subject>Nucleotide sequence</subject><subject>Optic nerve</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk analysis</subject><subject>Risk Factors</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Single-nucleotide polymorphism</subject><subject>Spinal cord</subject><subject>Systemic lupus erythematosus</subject><subject>Whole Genome Sequencing - methods</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9kk1v1DAQhiMEolXpH-CALHHhkmJ7HMe-IFUVH5UqcQGuluOMt16SeLGTov33eJu2tBzwxSPPO4_nq6peM3rGKKj3WTAh25oyVVMBwGt4Vh1zKljNWg7PH9lH1WnOW1oOaKaEeFkdcd1K3XB5XP04J7-v44D1Bqc4Isn4a8HJFWNe-j0JPU5z8AEzKQKcgyMp5J_EWzfHlImPiUy4pDjucQhzyCTuisi-ql54O2Q8vbtPqu-fPn67-FJfff18eXF-VTtJ5VxbpB12AL5lynLWgxA967VTTFonoGPcdkxT1wlJkaF3mulShKDOslZJCyfV5crto92aXQqjTXsTbTC3DzFtjE0loQEN1W0HngoHjRKFZkGC7z1ve9VwwZrC-rCydks3Yu9K5ckOT6BPPVO4Npt4YxrdNJoeAO_uACmWLubZjCE7HAY7YVyyKROhrWQgZZG-_Ue6jUuaSquKCrQCLtQByFeVSzHnhP4hGUbNYQvMugWmbIG53QIDJejN4zIeQu5nXgSwCnJxTRtMf__-D_YPefG9VA</recordid><startdate>20180516</startdate><enddate>20180516</enddate><creator>Estrada, Karol</creator><creator>Whelan, Christopher W.</creator><creator>Zhao, Fengmei</creator><creator>Bronson, Paola</creator><creator>Handsaker, Robert E.</creator><creator>Sun, Chao</creator><creator>Carulli, John P.</creator><creator>Harris, Tim</creator><creator>Ransohoff, Richard M.</creator><creator>McCarroll, Steven A.</creator><creator>Day-Williams, Aaron G.</creator><creator>Greenberg, Benjamin M.</creator><creator>MacArthur, Daniel G.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>SOI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3128-3547</orcidid><orcidid>https://orcid.org/0000-0003-0175-6910</orcidid><orcidid>https://orcid.org/0000-0001-8446-8468</orcidid></search><sort><creationdate>20180516</creationdate><title>A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c606t-ae0beb33f718a21d344d1d9c816ac43b12ab190cb460e1efc91939140ca1786a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>45</topic><topic>45/23</topic><topic>631/208/205/2138</topic><topic>631/250/371</topic><topic>692/699/249/1313</topic><topic>692/699/375/1411</topic><topic>Adult</topic><topic>Aquaporin 4</topic><topic>Aquaporin 4 - 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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.
Neuromyelitis optica (NMO) is a rare autoimmune condition characterized by inflammation and demyelination of the optic nerve and the spinal cord. Here, Estrada et al. identify NMO susceptibility variants in the MHC region and find that autoantibody-positive NMO genetically overlaps with lupus.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29769526</pmid><doi>10.1038/s41467-018-04332-3</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-3128-3547</orcidid><orcidid>https://orcid.org/0000-0003-0175-6910</orcidid><orcidid>https://orcid.org/0000-0001-8446-8468</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 45 45/23 631/208/205/2138 631/250/371 692/699/249/1313 692/699/375/1411 Adult Aquaporin 4 Aquaporin 4 - immunology Autoantibodies Autoimmune diseases Chronic conditions Copy number DNA Copy Number Variations Etiology Female Gene sequencing Genetic diversity Genetic Predisposition to Disease - genetics Genetic variance Genomes Haplotypes Humanities and Social Sciences Humans Immunoglobulin G Immunoglobulin G - immunology Major histocompatibility complex Major Histocompatibility Complex - genetics Male Middle Aged multidisciplinary Multiple sclerosis Neuromyelitis Neuromyelitis Optica - genetics Neuromyelitis Optica - immunology Nucleotide sequence Optic nerve Polymorphism, Single Nucleotide Risk analysis Risk Factors Science Science (multidisciplinary) Single-nucleotide polymorphism Spinal cord Systemic lupus erythematosus Whole Genome Sequencing - methods |
| title | A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T15%3A49%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20whole-genome%20sequence%20study%20identifies%20genetic%20risk%20factors%20for%20neuromyelitis%20optica&rft.jtitle=Nature%20communications&rft.au=Estrada,%20Karol&rft.date=2018-05-16&rft.volume=9&rft.issue=1&rft.spage=1929&rft.epage=10&rft.pages=1929-10&rft.artnum=1929&rft.issn=2041-1723&rft.eissn=2041-1723&rft_id=info:doi/10.1038/s41467-018-04332-3&rft_dat=%3Cproquest_doaj_%3E2040761366%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c606t-ae0beb33f718a21d344d1d9c816ac43b12ab190cb460e1efc91939140ca1786a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2039832485&rft_id=info:pmid/29769526&rfr_iscdi=true |