Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.3/3995 |
Resumo: | Background: Prior genome-scans of bipolar disorder have revealed chromosome 6q22 as a promising candidate region. However, linkage disequilibrium (LD) mapping studies have yet to identify replicated susceptibility loci. Methods: We analyzed 1,422 LD-tagging single nucleotide polymorphisms (SNPs) in 83 genes to test single-marker and locus-wide evidence of association with bipolar disorder in the NIMH Genetics Initiative bipolar pedigrees and the Portuguese Island Collection (PIC) (N = 1,093 in 528 informative pairs). Both studies previously demonstrated significant evidence of linkage to 6q. SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Evidence of single-marker association was assessed using the generalized disequilibrium test (GDT). Empirical estimates of gene-wide significance were obtained by permutation (via 100,000 gene-dropping simulations) of Fisher's combined test of P-values for each locus. Results: No single variant yielded significant experiment-wide evidence of association, for either the combined sample or in each subsample. Our gene-dropping simulations identified nominally significant gene-wide associations with multiple loci, of which NT5DC1 in the NIMH subsample and CCNC in the PIC were the strongest candidates. However, no one gene consistently exceeded empirical significance criteria in both independent samples or survived Bonferroni correction for the number of genes tested. Conclusions: Using a gene-based approach to family-based association, we identified gene-wide associations with several genes, though no single locus was significantly associated with bipolar disorder in both cohorts. This suggests that chromosome 6q may harbor multiple susceptibility loci or that complex patterns of LD in this region may confound approaches based on common SNPs. |
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Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization AlgorithmBipolar DisorderGenetic AssociationBackground: Prior genome-scans of bipolar disorder have revealed chromosome 6q22 as a promising candidate region. However, linkage disequilibrium (LD) mapping studies have yet to identify replicated susceptibility loci. Methods: We analyzed 1,422 LD-tagging single nucleotide polymorphisms (SNPs) in 83 genes to test single-marker and locus-wide evidence of association with bipolar disorder in the NIMH Genetics Initiative bipolar pedigrees and the Portuguese Island Collection (PIC) (N = 1,093 in 528 informative pairs). Both studies previously demonstrated significant evidence of linkage to 6q. SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Evidence of single-marker association was assessed using the generalized disequilibrium test (GDT). Empirical estimates of gene-wide significance were obtained by permutation (via 100,000 gene-dropping simulations) of Fisher's combined test of P-values for each locus. Results: No single variant yielded significant experiment-wide evidence of association, for either the combined sample or in each subsample. Our gene-dropping simulations identified nominally significant gene-wide associations with multiple loci, of which NT5DC1 in the NIMH subsample and CCNC in the PIC were the strongest candidates. However, no one gene consistently exceeded empirical significance criteria in both independent samples or survived Bonferroni correction for the number of genes tested. Conclusions: Using a gene-based approach to family-based association, we identified gene-wide associations with several genes, though no single locus was significantly associated with bipolar disorder in both cohorts. This suggests that chromosome 6q may harbor multiple susceptibility loci or that complex patterns of LD in this region may confound approaches based on common SNPs.John Wiley and SonsRepositório da Universidade dos AçoresBigdeli, BernardMaher, Brion S.Zhao, ZhongmingSun, JingchunMedeiros, HelenaAkula, NirmalaMcMahon, Francis J.Carvalho, CéliaFerreira, Susana R.Azevedo, Maria H.Knowles, James A.Pato, Michele T.Pato, Carlos N.Fanous, Ayman H.2017-02-23T18:36:22Z2013-122013-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.3/3995engBigdeli, T.B., Maher, B., Zhao, Z., Sun, ,J., Amdur, R., Medeiros, H., Akula, N., McMahon, F., Barreto Carvalho, C., Ferreira, R., Azevedo, M.H., Knowles, J., Pato,M., Pato, C.N., Fanous, A. (2013). Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm. "American Journal of Medical Genetics Part B: Neuropsychiatric Genetics", 162(8), 898-906.1552-485X10.1002/ajmg.b.32200metadata only accessinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-12-20T14:32:11Zoai:repositorio.uac.pt:10400.3/3995Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:26:31.071056Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm |
title |
Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm |
spellingShingle |
Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm Bigdeli, Bernard Bipolar Disorder Genetic Association |
title_short |
Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm |
title_full |
Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm |
title_fullStr |
Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm |
title_full_unstemmed |
Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm |
title_sort |
Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm |
author |
Bigdeli, Bernard |
author_facet |
Bigdeli, Bernard Maher, Brion S. Zhao, Zhongming Sun, Jingchun Medeiros, Helena Akula, Nirmala McMahon, Francis J. Carvalho, Célia Ferreira, Susana R. Azevedo, Maria H. Knowles, James A. Pato, Michele T. Pato, Carlos N. Fanous, Ayman H. |
author_role |
author |
author2 |
Maher, Brion S. Zhao, Zhongming Sun, Jingchun Medeiros, Helena Akula, Nirmala McMahon, Francis J. Carvalho, Célia Ferreira, Susana R. Azevedo, Maria H. Knowles, James A. Pato, Michele T. Pato, Carlos N. Fanous, Ayman H. |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade dos Açores |
dc.contributor.author.fl_str_mv |
Bigdeli, Bernard Maher, Brion S. Zhao, Zhongming Sun, Jingchun Medeiros, Helena Akula, Nirmala McMahon, Francis J. Carvalho, Célia Ferreira, Susana R. Azevedo, Maria H. Knowles, James A. Pato, Michele T. Pato, Carlos N. Fanous, Ayman H. |
dc.subject.por.fl_str_mv |
Bipolar Disorder Genetic Association |
topic |
Bipolar Disorder Genetic Association |
description |
Background: Prior genome-scans of bipolar disorder have revealed chromosome 6q22 as a promising candidate region. However, linkage disequilibrium (LD) mapping studies have yet to identify replicated susceptibility loci. Methods: We analyzed 1,422 LD-tagging single nucleotide polymorphisms (SNPs) in 83 genes to test single-marker and locus-wide evidence of association with bipolar disorder in the NIMH Genetics Initiative bipolar pedigrees and the Portuguese Island Collection (PIC) (N = 1,093 in 528 informative pairs). Both studies previously demonstrated significant evidence of linkage to 6q. SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Evidence of single-marker association was assessed using the generalized disequilibrium test (GDT). Empirical estimates of gene-wide significance were obtained by permutation (via 100,000 gene-dropping simulations) of Fisher's combined test of P-values for each locus. Results: No single variant yielded significant experiment-wide evidence of association, for either the combined sample or in each subsample. Our gene-dropping simulations identified nominally significant gene-wide associations with multiple loci, of which NT5DC1 in the NIMH subsample and CCNC in the PIC were the strongest candidates. However, no one gene consistently exceeded empirical significance criteria in both independent samples or survived Bonferroni correction for the number of genes tested. Conclusions: Using a gene-based approach to family-based association, we identified gene-wide associations with several genes, though no single locus was significantly associated with bipolar disorder in both cohorts. This suggests that chromosome 6q may harbor multiple susceptibility loci or that complex patterns of LD in this region may confound approaches based on common SNPs. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-12 2013-12-01T00:00:00Z 2017-02-23T18:36:22Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.3/3995 |
url |
http://hdl.handle.net/10400.3/3995 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bigdeli, T.B., Maher, B., Zhao, Z., Sun, ,J., Amdur, R., Medeiros, H., Akula, N., McMahon, F., Barreto Carvalho, C., Ferreira, R., Azevedo, M.H., Knowles, J., Pato,M., Pato, C.N., Fanous, A. (2013). Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm. "American Journal of Medical Genetics Part B: Neuropsychiatric Genetics", 162(8), 898-906. 1552-485X 10.1002/ajmg.b.32200 |
dc.rights.driver.fl_str_mv |
metadata only access info:eu-repo/semantics/openAccess |
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metadata only access |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
John Wiley and Sons |
publisher.none.fl_str_mv |
John Wiley and Sons |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799130718143512576 |