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Association Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithm

2013-12Journal article Restricted access
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dc.contributor.authorBigdeli, Bernard
dc.contributor.authorMaher, Brion S.
dc.contributor.authorZhao, Zhongming
dc.contributor.authorSun, Jingchun
dc.contributor.authorMedeiros, Helena
dc.contributor.authorAkula, Nirmala
dc.contributor.authorMcMahon, Francis J.
dc.contributor.authorCarvalho, Célia
dc.contributor.authorFerreira, Susana R.
dc.contributor.authorAzevedo, Maria H.
dc.contributor.authorKnowles, James A.
dc.contributor.authorPato, Michele T.
dc.contributor.authorPato, Carlos N.
dc.contributor.authorFanous, Ayman H.
dc.date.accessioned2017-02-23T18:36:22Z
dc.date.available2017-02-23T18:36:22Z
dc.date.issued2013-12
dc.description.abstractBackground: 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.en
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBigdeli, 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.en
dc.identifier.doi10.1002/ajmg.b.32200pt_PT
dc.identifier.issn1552-485X
dc.identifier.urihttp://hdl.handle.net/10400.3/3995
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley and Sonspt_PT
dc.relation.publisherversionhttp://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.32200/fullpt_PT
dc.subjectBipolar Disorderen
dc.subjectGenetic Associationen
dc.titleAssociation Study of 83 Candidate Genes for Bipolar Disorder in Chromosome 6q Selected Using an Evidence-Based Prioritization Algorithmen
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage906pt_PT
oaire.citation.issue(8)pt_PT
oaire.citation.startPage898pt_PT
oaire.citation.titleAmerican Journal of Medical Genetics Part B: Neuropsychiatric Geneticsen
oaire.citation.volume162pt_PT
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT

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