Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE)
We recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported a...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2009
- Institución:
- Universidad del Rosario
- Repositorio:
- Repositorio EdocUR - U. Rosario
- Idioma:
- eng
- OAI Identifier:
- oai:repository.urosario.edu.co:10336/24221
- Acceso en línea:
- https://doi.org/10.1093/hmg/ddp007
https://repository.urosario.edu.co/handle/10336/24221
- Palabra clave:
- Alpha integrin
Alpha m integrin
Alpha x integrin
Gene product
Integrin
Protein trim2
Unclassified drug
African american
Article
Controlled study
European american
Exon
Female
Gene frequency
Gene replication
Gene structure
Genetic association
Genetic code
Genetic susceptibility
Genetic variability
Geographic distribution
Geographic origin
Haplotype
Human
Japan
Korea
Major clinical study
Male
Priority journal
Race difference
Systemic lupus erythematosus
Alleles
Antigens, cd11b
Asian continental ancestry group
Bayes theorem
Case-control studies
Colombia
Demography
European continental ancestry group
Female
Genetic predisposition to disease
Great britain
Haplotypes
Hispanic americans
Humans
Japan
Korea
Linkage disequilibrium
Male
Meta-analysis as topic
Mexico
Reproducibility of results
systemic
single nucleotide
Lupus erythematosus
Polymorphism
- Rights
- License
- Abierto (Texto Completo)
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dc.title.spa.fl_str_mv |
Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) |
title |
Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) |
spellingShingle |
Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) Alpha integrin Alpha m integrin Alpha x integrin Gene product Integrin Protein trim2 Unclassified drug African american Article Controlled study European american Exon Female Gene frequency Gene replication Gene structure Genetic association Genetic code Genetic susceptibility Genetic variability Geographic distribution Geographic origin Haplotype Human Japan Korea Major clinical study Male Priority journal Race difference Systemic lupus erythematosus Alleles Antigens, cd11b Asian continental ancestry group Bayes theorem Case-control studies Colombia Demography European continental ancestry group Female Genetic predisposition to disease Great britain Haplotypes Hispanic americans Humans Japan Korea Linkage disequilibrium Male Meta-analysis as topic Mexico Reproducibility of results systemic single nucleotide Lupus erythematosus Polymorphism |
title_short |
Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) |
title_full |
Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) |
title_fullStr |
Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) |
title_full_unstemmed |
Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) |
title_sort |
Evaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE) |
dc.subject.keyword.spa.fl_str_mv |
Alpha integrin Alpha m integrin Alpha x integrin Gene product Integrin Protein trim2 Unclassified drug African american Article Controlled study European american Exon Female Gene frequency Gene replication Gene structure Genetic association Genetic code Genetic susceptibility Genetic variability Geographic distribution Geographic origin Haplotype Human Japan Korea Major clinical study Male Priority journal Race difference Systemic lupus erythematosus Alleles Antigens, cd11b Asian continental ancestry group Bayes theorem Case-control studies Colombia Demography European continental ancestry group Female Genetic predisposition to disease Great britain Haplotypes Hispanic americans Humans Japan Korea Linkage disequilibrium Male Meta-analysis as topic Mexico Reproducibility of results |
topic |
Alpha integrin Alpha m integrin Alpha x integrin Gene product Integrin Protein trim2 Unclassified drug African american Article Controlled study European american Exon Female Gene frequency Gene replication Gene structure Genetic association Genetic code Genetic susceptibility Genetic variability Geographic distribution Geographic origin Haplotype Human Japan Korea Major clinical study Male Priority journal Race difference Systemic lupus erythematosus Alleles Antigens, cd11b Asian continental ancestry group Bayes theorem Case-control studies Colombia Demography European continental ancestry group Female Genetic predisposition to disease Great britain Haplotypes Hispanic americans Humans Japan Korea Linkage disequilibrium Male Meta-analysis as topic Mexico Reproducibility of results systemic single nucleotide Lupus erythematosus Polymorphism |
dc.subject.keyword.eng.fl_str_mv |
systemic single nucleotide Lupus erythematosus Polymorphism |
description |
We recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported an association between SLE susceptibility and ITGAM or ITGAM-ITGAX region. The primary objectives of this study are to assess whether single or multiple causal variants from the same gene or any nearby gene(s) are involved in SLE susceptibility and to confirm a robust ITGAM association across nine independent data sets (n = 8211). First, we confirmed our previously reported association of rs1143679 (risk allele 'A') with SLE in EAs (P = 1.0 × 10-8) and Hispanic-Americans (P = 2.9 × 10-5). Secondly, using a comprehensive imputation-based association test, we found that ITGAM is one of the major non-human leukocyte antigen susceptibility genes for SLE, and the strongest association for EA is the same coding variant rs1143679 (log10Bayes factor=20, P = 6.17 × 10-24). Thirdly, we determined the robustness of rs1143679 association with SLE across three additional case-control samples, including UK (P = 6.2 × 10-8), Colombian (P = 3.6 × 10-7), Mexican (P = 0.002), as well as two independent sets of trios from UK (P TDT = 1.4 × 10-5) and Mexico (P TDT = 0.015). A meta-analysis combing all independent data sets greatly reinforces the association (P meta = 7.1 × 10-50, odds ratio = 1.83, 95% confidence interval = 1.69-1.98, n = 10 046). However, this ITGAM association was not observed in the Korean or Japanese samples, in which rs1143679 is monomorphic for the non-risk allele (G). Taken together along with our earlier findings, these results demonstrate that the coding variant, rs1143679, best explains the ITGAM- SLE association, especially in European- and African-derived populations, but not in Asian populations. © The Author 2009. Published by Oxford University Press. All rights reserved. |
publishDate |
2009 |
dc.date.created.spa.fl_str_mv |
2009 |
dc.date.accessioned.none.fl_str_mv |
2020-05-26T00:10:16Z |
dc.date.available.none.fl_str_mv |
2020-05-26T00:10:16Z |
dc.type.eng.fl_str_mv |
article |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.spa.spa.fl_str_mv |
Artículo |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1093/hmg/ddp007 |
dc.identifier.issn.none.fl_str_mv |
14602083 09646906 |
dc.identifier.uri.none.fl_str_mv |
https://repository.urosario.edu.co/handle/10336/24221 |
url |
https://doi.org/10.1093/hmg/ddp007 https://repository.urosario.edu.co/handle/10336/24221 |
identifier_str_mv |
14602083 09646906 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.relation.citationEndPage.none.fl_str_mv |
1180 |
dc.relation.citationIssue.none.fl_str_mv |
No. 6 |
dc.relation.citationStartPage.none.fl_str_mv |
1171 |
dc.relation.citationTitle.none.fl_str_mv |
Human Molecular Genetics |
dc.relation.citationVolume.none.fl_str_mv |
Vol. 18 |
dc.relation.ispartof.spa.fl_str_mv |
Human Molecular Genetics, ISSN:14602083, 09646906, Vol.18, No.6 (2009); pp. 1171-1180 |
dc.relation.uri.spa.fl_str_mv |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-61849093275&doi=10.1093%2fhmg%2fddp007&partnerID=40&md5=4455104b301546fe8dfcaa6e5b03c9b3 |
dc.rights.coar.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.acceso.spa.fl_str_mv |
Abierto (Texto Completo) |
rights_invalid_str_mv |
Abierto (Texto Completo) http://purl.org/coar/access_right/c_abf2 |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
institution |
Universidad del Rosario |
dc.source.instname.spa.fl_str_mv |
instname:Universidad del Rosario |
dc.source.reponame.spa.fl_str_mv |
reponame:Repositorio Institucional EdocUR |
repository.name.fl_str_mv |
Repositorio institucional EdocUR |
repository.mail.fl_str_mv |
edocur@urosario.edu.co |
_version_ |
1814167642474283008 |
spelling |
dbc82f9b-3284-4238-910c-9caa2e2bd7fe5a1d2b19-ce5a-49e8-bd50-6bd90a8463c61bb4adfb-6739-43ca-9f49-52081d3806adfe754265-ebb1-45e5-91e5-ab9646cd14d6fc2efb80-a632-4403-96f5-09334465216834b38e53-a3b1-4101-a8df-21cac0cb931694055d74-99fd-44c1-b7e6-0c05eebc5e4f06d736b0-74df-4660-b37e-3a005f8732a5a31b61a8-a6ee-4d79-9724-0bacdbc1e6cf522497011211d0da-5453-4a3b-a0e8-36c40d3026e47b586728-5baa-4b09-b428-7bf35c3520016b892963-5ceb-441c-93d0-96e93ace8d07a80e008c-7f0d-4fa9-937b-646778f7a2951a5b059f-395c-4c61-b489-210c7b8c6dcfef52afb8-0580-4dde-bb9c-53dbf521427b8413200a-d245-4a47-9bf8-a656d5ac34ae745e1f5a-a9e9-4bc2-b74c-b681dc65c7583568b65a-bc38-49f5-b7fa-4291ae155adb19fa32b9-3bc1-446c-a582-50f1e4bf7acbc4bfdc11-7dbd-4d4e-b73c-9064278d4f277db99122-14fd-4cf7-8433-c6ea25aac95377a5629b-b50e-4af5-811e-968398e409d419474778600ee2b0a18-7380-46ca-8efb-e4f1faeaaa52a2a840f2-1bd0-4d31-a198-4523d887d96c747a926d-a3cb-4aef-b6f0-56f49721456a41f8164b-3ecf-4dc5-ad77-a3580104bd352020-05-26T00:10:16Z2020-05-26T00:10:16Z2009We recently identified a novel non-synonymous variant, rs1143679, at exon 3 of the ITGAM gene associated with systemic lupus erythematosus (SLE) susceptibility in European-Americans (EAs) and African-Americans. Using genome-wide association approach, three other studies also independently reported an association between SLE susceptibility and ITGAM or ITGAM-ITGAX region. The primary objectives of this study are to assess whether single or multiple causal variants from the same gene or any nearby gene(s) are involved in SLE susceptibility and to confirm a robust ITGAM association across nine independent data sets (n = 8211). First, we confirmed our previously reported association of rs1143679 (risk allele 'A') with SLE in EAs (P = 1.0 × 10-8) and Hispanic-Americans (P = 2.9 × 10-5). Secondly, using a comprehensive imputation-based association test, we found that ITGAM is one of the major non-human leukocyte antigen susceptibility genes for SLE, and the strongest association for EA is the same coding variant rs1143679 (log10Bayes factor=20, P = 6.17 × 10-24). Thirdly, we determined the robustness of rs1143679 association with SLE across three additional case-control samples, including UK (P = 6.2 × 10-8), Colombian (P = 3.6 × 10-7), Mexican (P = 0.002), as well as two independent sets of trios from UK (P TDT = 1.4 × 10-5) and Mexico (P TDT = 0.015). A meta-analysis combing all independent data sets greatly reinforces the association (P meta = 7.1 × 10-50, odds ratio = 1.83, 95% confidence interval = 1.69-1.98, n = 10 046). However, this ITGAM association was not observed in the Korean or Japanese samples, in which rs1143679 is monomorphic for the non-risk allele (G). Taken together along with our earlier findings, these results demonstrate that the coding variant, rs1143679, best explains the ITGAM- SLE association, especially in European- and African-derived populations, but not in Asian populations. © The Author 2009. Published by Oxford University Press. All rights reserved.application/pdfhttps://doi.org/10.1093/hmg/ddp0071460208309646906https://repository.urosario.edu.co/handle/10336/24221eng1180No. 61171Human Molecular GeneticsVol. 18Human Molecular Genetics, ISSN:14602083, 09646906, Vol.18, No.6 (2009); pp. 1171-1180https://www.scopus.com/inward/record.uri?eid=2-s2.0-61849093275&doi=10.1093%2fhmg%2fddp007&partnerID=40&md5=4455104b301546fe8dfcaa6e5b03c9b3Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURAlpha integrinAlpha m integrinAlpha x integrinGene productIntegrinProtein trim2Unclassified drugAfrican americanArticleControlled studyEuropean americanExonFemaleGene frequencyGene replicationGene structureGenetic associationGenetic codeGenetic susceptibilityGenetic variabilityGeographic distributionGeographic originHaplotypeHumanJapanKoreaMajor clinical studyMalePriority journalRace differenceSystemic lupus erythematosusAllelesAntigens, cd11bAsian continental ancestry groupBayes theoremCase-control studiesColombiaDemographyEuropean continental ancestry groupFemaleGenetic predisposition to diseaseGreat britainHaplotypesHispanic americansHumansJapanKoreaLinkage disequilibriumMaleMeta-analysis as topicMexicoReproducibility of resultssystemicsingle nucleotideLupus erythematosusPolymorphismEvaluation of imputation-based association in and around the integrin-?-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE)articleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501Han, ShizhongKim-Howard, XanaDeshmukh, HarshalKamatani, YoichiroViswanathan, ParvathiGuthridge, Joel M.Thomas, KenazKaufman, Kenneth M.Ojwang, JoshuaRojas-Villarraga, AdrianaBaca, VicenteOrozco, LorenaRhodes, BenjaminChoi, Chan-BumGregersen, Peter K.Merrill, Joan T.James, Judith A.Gaffney, Patrick M.Moser, Kathy L.Jacob, Chaim O.Kimberly, Robert P.Harley, John B.Bae, Sang-ChoelAnaya, Juan-ManuelAlarcón-Riquelme, Marta E.Matsuda, KoichiVyse, Timothy J.Nath, Swapan K.10336/24221oai:repository.urosario.edu.co:10336/242212022-05-02 07:37:13.581094https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co |