Multilocus evaluation of genetic predictors of multiple sclerosis
[Display omitted] •Largest-to-date study of GWAS signals of multiple sclerosis (MS) in Russian population.•Associations with MS replicated for the INAVA, EOMES, C6orf10, CD86, and GPR65 loci.•Strongest association detected for rs3129934 in the major histocompatibility region.•C6orf10*T/T + STAT3*T c...
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| Veröffentlicht in: | Gene 2022-01, Vol.809, p.146008-146008, Article 146008 |
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| creator | Timasheva, Yanina Nasibullin, Timur R. Tuktarova, Ilsiyar A. Erdman, Vera V. Galiullin, Timur R. Zaplakhova, Oksana V. Bakhtiiarova, Klara Z. |
| description | [Display omitted]
•Largest-to-date study of GWAS signals of multiple sclerosis (MS) in Russian population.•Associations with MS replicated for the INAVA, EOMES, C6orf10, CD86, and GPR65 loci.•Strongest association detected for rs3129934 in the major histocompatibility region.•C6orf10*T/T + STAT3*T combination is associated with the highest risk of MS for women.•C6orf10*T + EOMES*C + RPS6KB1*C conferred the highest MS risk for men.
Genome-wide association studies identified numerous susceptibility loci for multiple sclerosis in populations of European ancestry, but the associations are not always reproducible in other populations due to admixture and different linkage disequilibrium patterns obscuring true association signals.
Our aim was to identify genetic predictors of multiple sclerosis in three ethnically homogenous populations from the Volga-Ural region of Russian Federation.
In the largest to date study of multiple sclerosis in Russian population, involving 2048 participants from the Republic of Bashkortostan, Russian Federation (641 patients with multiple sclerosis and 1407 unaffected individuals), we performed replication analysis of previously identified genome-wide signals for multiple sclerosis. Associations were tested using logistic regression analysis under additive genetic model adjusted for sex. Meta-analysis of the study results in three populations was performed under fixed effects and random effects models.
We demonstrate the association with multiple sclerosis of the five variants (INAVA rs7522462, EOMES rs11129295, C6orf10 rs3129934, CD86 rs9282641, and GPR65 rs2119704). The strongest association (OR = 2.16, CI:1.85–2.74, P = 2.53x10−13) was detected for rs3129934 polymorphism in the major histocompatibility region. Multilocus analysis has revealed 322 and 27 allelic patterns associated with multiple sclerosis in women and men, respectively. In women, the highest risk of MS was conferred by C6orf10 rs3129934*T/T + STAT3 rs744166*T combination (OR = 11.87), in men – by C6orf10 rs3129934*T + EOMES rs11129295*C + RPS6KB1 rs180515*C combination (OR = 3.25).
We confirm five associations with multiple sclerosis previously reported in genome-wide scans in Europeans in three ethnic groups from the Volga-Ural region of Russia. |
| doi_str_mv | 10.1016/j.gene.2021.146008 |
| format | Article |
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•Largest-to-date study of GWAS signals of multiple sclerosis (MS) in Russian population.•Associations with MS replicated for the INAVA, EOMES, C6orf10, CD86, and GPR65 loci.•Strongest association detected for rs3129934 in the major histocompatibility region.•C6orf10*T/T + STAT3*T combination is associated with the highest risk of MS for women.•C6orf10*T + EOMES*C + RPS6KB1*C conferred the highest MS risk for men.
Genome-wide association studies identified numerous susceptibility loci for multiple sclerosis in populations of European ancestry, but the associations are not always reproducible in other populations due to admixture and different linkage disequilibrium patterns obscuring true association signals.
Our aim was to identify genetic predictors of multiple sclerosis in three ethnically homogenous populations from the Volga-Ural region of Russian Federation.
In the largest to date study of multiple sclerosis in Russian population, involving 2048 participants from the Republic of Bashkortostan, Russian Federation (641 patients with multiple sclerosis and 1407 unaffected individuals), we performed replication analysis of previously identified genome-wide signals for multiple sclerosis. Associations were tested using logistic regression analysis under additive genetic model adjusted for sex. Meta-analysis of the study results in three populations was performed under fixed effects and random effects models.
We demonstrate the association with multiple sclerosis of the five variants (INAVA rs7522462, EOMES rs11129295, C6orf10 rs3129934, CD86 rs9282641, and GPR65 rs2119704). The strongest association (OR = 2.16, CI:1.85–2.74, P = 2.53x10−13) was detected for rs3129934 polymorphism in the major histocompatibility region. Multilocus analysis has revealed 322 and 27 allelic patterns associated with multiple sclerosis in women and men, respectively. In women, the highest risk of MS was conferred by C6orf10 rs3129934*T/T + STAT3 rs744166*T combination (OR = 11.87), in men – by C6orf10 rs3129934*T + EOMES rs11129295*C + RPS6KB1 rs180515*C combination (OR = 3.25).
We confirm five associations with multiple sclerosis previously reported in genome-wide scans in Europeans in three ethnic groups from the Volga-Ural region of Russia.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2021.146008</identifier><identifier>PMID: 34656742</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; B7-2 Antigen - genetics ; Bashkiria - ethnology ; Carrier Proteins - genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genome-wide association signals ; Human leukocyte antigen ; Humans ; Major histocompatibility region ; Male ; Middle Aged ; Multiple sclerosis ; Multiple Sclerosis - etiology ; Multiple Sclerosis - genetics ; Polymorphism, Single Nucleotide - genetics ; Receptors, G-Protein-Coupled - genetics ; Rs3129934 ; T-Box Domain Proteins - genetics</subject><ispartof>Gene, 2022-01, Vol.809, p.146008-146008, Article 146008</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-65c9123790d4707313f6ae459132e4576b6c90bd7413c3e01596a5d65632fe223</citedby><cites>FETCH-LOGICAL-c356t-65c9123790d4707313f6ae459132e4576b6c90bd7413c3e01596a5d65632fe223</cites><orcidid>0000-0002-9918-6962</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.gene.2021.146008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34656742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Timasheva, Yanina</creatorcontrib><creatorcontrib>Nasibullin, Timur R.</creatorcontrib><creatorcontrib>Tuktarova, Ilsiyar A.</creatorcontrib><creatorcontrib>Erdman, Vera V.</creatorcontrib><creatorcontrib>Galiullin, Timur R.</creatorcontrib><creatorcontrib>Zaplakhova, Oksana V.</creatorcontrib><creatorcontrib>Bakhtiiarova, Klara Z.</creatorcontrib><title>Multilocus evaluation of genetic predictors of multiple sclerosis</title><title>Gene</title><addtitle>Gene</addtitle><description>[Display omitted]
•Largest-to-date study of GWAS signals of multiple sclerosis (MS) in Russian population.•Associations with MS replicated for the INAVA, EOMES, C6orf10, CD86, and GPR65 loci.•Strongest association detected for rs3129934 in the major histocompatibility region.•C6orf10*T/T + STAT3*T combination is associated with the highest risk of MS for women.•C6orf10*T + EOMES*C + RPS6KB1*C conferred the highest MS risk for men.
Genome-wide association studies identified numerous susceptibility loci for multiple sclerosis in populations of European ancestry, but the associations are not always reproducible in other populations due to admixture and different linkage disequilibrium patterns obscuring true association signals.
Our aim was to identify genetic predictors of multiple sclerosis in three ethnically homogenous populations from the Volga-Ural region of Russian Federation.
In the largest to date study of multiple sclerosis in Russian population, involving 2048 participants from the Republic of Bashkortostan, Russian Federation (641 patients with multiple sclerosis and 1407 unaffected individuals), we performed replication analysis of previously identified genome-wide signals for multiple sclerosis. Associations were tested using logistic regression analysis under additive genetic model adjusted for sex. Meta-analysis of the study results in three populations was performed under fixed effects and random effects models.
We demonstrate the association with multiple sclerosis of the five variants (INAVA rs7522462, EOMES rs11129295, C6orf10 rs3129934, CD86 rs9282641, and GPR65 rs2119704). The strongest association (OR = 2.16, CI:1.85–2.74, P = 2.53x10−13) was detected for rs3129934 polymorphism in the major histocompatibility region. Multilocus analysis has revealed 322 and 27 allelic patterns associated with multiple sclerosis in women and men, respectively. In women, the highest risk of MS was conferred by C6orf10 rs3129934*T/T + STAT3 rs744166*T combination (OR = 11.87), in men – by C6orf10 rs3129934*T + EOMES rs11129295*C + RPS6KB1 rs180515*C combination (OR = 3.25).
We confirm five associations with multiple sclerosis previously reported in genome-wide scans in Europeans in three ethnic groups from the Volga-Ural region of Russia.</description><subject>Adult</subject><subject>B7-2 Antigen - genetics</subject><subject>Bashkiria - ethnology</subject><subject>Carrier Proteins - genetics</subject><subject>Case-Control Studies</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-wide association signals</subject><subject>Human leukocyte antigen</subject><subject>Humans</subject><subject>Major histocompatibility region</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - etiology</subject><subject>Multiple Sclerosis - genetics</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Rs3129934</subject><subject>T-Box Domain Proteins - genetics</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMo7rr6BzxIj15a89EkLXhZFr9gxYueQzedSpa0qUm74L83patH5zIwPPMy8yB0TXBGMBF3--wTOsgopiQjucC4OEFLUsgyxZgVp2iJmSxSQki5QBch7HEszuk5WrBccCFzukTr19EOxjo9hgQOlR2rwbgucU0yZQ9GJ72H2ujB-TBN2wnvLSRBW_AumHCJzprKBrg69hX6eHx43zyn27enl816m2rGxZAKrktCmSxxnUssGWGNqCDnJWE0Nil2Qpd4V8ucMM0AE16KitfxTkYboJSt0O2c23v3NUIYVGuCBmurDtwYFOUFY1RKNqF0RnW8MHhoVO9NW_lvRbCa1Km9mt5Tkzo1q4tLN8f8cddC_bfy6yoC9zMA8cuDAa-CNtDpqMeDHlTtzH_5P0Jefg8</recordid><startdate>20220130</startdate><enddate>20220130</enddate><creator>Timasheva, Yanina</creator><creator>Nasibullin, Timur R.</creator><creator>Tuktarova, Ilsiyar A.</creator><creator>Erdman, Vera V.</creator><creator>Galiullin, Timur R.</creator><creator>Zaplakhova, Oksana V.</creator><creator>Bakhtiiarova, Klara Z.</creator><general>Elsevier B.V</general><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>7X8</scope><orcidid>https://orcid.org/0000-0002-9918-6962</orcidid></search><sort><creationdate>20220130</creationdate><title>Multilocus evaluation of genetic predictors of multiple sclerosis</title><author>Timasheva, Yanina ; Nasibullin, Timur R. ; Tuktarova, Ilsiyar A. ; Erdman, Vera V. ; Galiullin, Timur R. ; Zaplakhova, Oksana V. ; Bakhtiiarova, Klara Z.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-65c9123790d4707313f6ae459132e4576b6c90bd7413c3e01596a5d65632fe223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>B7-2 Antigen - genetics</topic><topic>Bashkiria - ethnology</topic><topic>Carrier Proteins - genetics</topic><topic>Case-Control Studies</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-wide association signals</topic><topic>Human leukocyte antigen</topic><topic>Humans</topic><topic>Major histocompatibility region</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis - etiology</topic><topic>Multiple Sclerosis - genetics</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Rs3129934</topic><topic>T-Box Domain Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Timasheva, Yanina</creatorcontrib><creatorcontrib>Nasibullin, Timur R.</creatorcontrib><creatorcontrib>Tuktarova, Ilsiyar A.</creatorcontrib><creatorcontrib>Erdman, Vera V.</creatorcontrib><creatorcontrib>Galiullin, Timur R.</creatorcontrib><creatorcontrib>Zaplakhova, Oksana V.</creatorcontrib><creatorcontrib>Bakhtiiarova, Klara Z.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Timasheva, Yanina</au><au>Nasibullin, Timur R.</au><au>Tuktarova, Ilsiyar A.</au><au>Erdman, Vera V.</au><au>Galiullin, Timur R.</au><au>Zaplakhova, Oksana V.</au><au>Bakhtiiarova, Klara Z.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multilocus evaluation of genetic predictors of multiple sclerosis</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2022-01-30</date><risdate>2022</risdate><volume>809</volume><spage>146008</spage><epage>146008</epage><pages>146008-146008</pages><artnum>146008</artnum><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>[Display omitted]
•Largest-to-date study of GWAS signals of multiple sclerosis (MS) in Russian population.•Associations with MS replicated for the INAVA, EOMES, C6orf10, CD86, and GPR65 loci.•Strongest association detected for rs3129934 in the major histocompatibility region.•C6orf10*T/T + STAT3*T combination is associated with the highest risk of MS for women.•C6orf10*T + EOMES*C + RPS6KB1*C conferred the highest MS risk for men.
Genome-wide association studies identified numerous susceptibility loci for multiple sclerosis in populations of European ancestry, but the associations are not always reproducible in other populations due to admixture and different linkage disequilibrium patterns obscuring true association signals.
Our aim was to identify genetic predictors of multiple sclerosis in three ethnically homogenous populations from the Volga-Ural region of Russian Federation.
In the largest to date study of multiple sclerosis in Russian population, involving 2048 participants from the Republic of Bashkortostan, Russian Federation (641 patients with multiple sclerosis and 1407 unaffected individuals), we performed replication analysis of previously identified genome-wide signals for multiple sclerosis. Associations were tested using logistic regression analysis under additive genetic model adjusted for sex. Meta-analysis of the study results in three populations was performed under fixed effects and random effects models.
We demonstrate the association with multiple sclerosis of the five variants (INAVA rs7522462, EOMES rs11129295, C6orf10 rs3129934, CD86 rs9282641, and GPR65 rs2119704). The strongest association (OR = 2.16, CI:1.85–2.74, P = 2.53x10−13) was detected for rs3129934 polymorphism in the major histocompatibility region. Multilocus analysis has revealed 322 and 27 allelic patterns associated with multiple sclerosis in women and men, respectively. In women, the highest risk of MS was conferred by C6orf10 rs3129934*T/T + STAT3 rs744166*T combination (OR = 11.87), in men – by C6orf10 rs3129934*T + EOMES rs11129295*C + RPS6KB1 rs180515*C combination (OR = 3.25).
We confirm five associations with multiple sclerosis previously reported in genome-wide scans in Europeans in three ethnic groups from the Volga-Ural region of Russia.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34656742</pmid><doi>10.1016/j.gene.2021.146008</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-9918-6962</orcidid></addata></record> |
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| subjects | Adult B7-2 Antigen - genetics Bashkiria - ethnology Carrier Proteins - genetics Case-Control Studies Female Genetic Predisposition to Disease Genome-wide association signals Human leukocyte antigen Humans Major histocompatibility region Male Middle Aged Multiple sclerosis Multiple Sclerosis - etiology Multiple Sclerosis - genetics Polymorphism, Single Nucleotide - genetics Receptors, G-Protein-Coupled - genetics Rs3129934 T-Box Domain Proteins - genetics |
| title | Multilocus evaluation of genetic predictors of multiple sclerosis |
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