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...

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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)
id EDOCUR2_ede6a2328156ff2e5448000b9f693326
oai_identifier_str oai:repository.urosario.edu.co:10336/24221
network_acronym_str EDOCUR2
network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
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
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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