View in EDS PDF Full Text

Poor replication of candidate genes for major depressive disorder using genome-wide association data.

Saved in:
Bibliographic Details
Title: Poor replication of candidate genes for major depressive disorder using genome-wide association data.
Authors: Bosker, F. J., Hartman, C. A., Nolte, I. M., Prins, B. P., Terpstra, P., Posthuma, D., van Veen, T., Willemsen, G., DeRijk, R. H., de Geus, E. J., Hoogendijk, W. J., Sullivan, P. F., Penninx, B. W., Boomsma, D. I., Snieder, H., Nolen, W. A.
Source: Molecular Psychiatry. May2011, Vol. 16 Issue 5, p516-532. 17p. 1 Diagram, 3 Charts, 3 Graphs.
Subjects: Mental depression, Genetic polymorphisms, DNA replication, Genes, Genotype-environment interaction
Abstract: Data from the Genetic Association Information Network (GAIN) genome-wide association study (GWAS) in major depressive disorder (MDD) were used to explore previously reported candidate gene and single-nucleotide polymorphism (SNP) associations in MDD. A systematic literature search of candidate genes associated with MDD in case-control studies was performed before the results of the GAIN MDD study became available. Measured and imputed candidate SNPs and genes were tested in the GAIN MDD study encompassing 1738 cases and 1802 controls. Imputation was used to increase the number of SNPs from the GWAS and to improve coverage of SNPs in the candidate genes selected. Tests were carried out for individual SNPs and the entire gene using different statistical approaches, with permutation analysis as the final arbiter. In all, 78 papers reporting on 57 genes were identified, from which 92 SNPs could be mapped. In the GAIN MDD study, two SNPs were associated with MDD: C5orf20 (rs12520799; P=0.038; odds ratio (OR) AT=1.10, 95% CI 0.95-1.29; OR TT=1.21, 95% confidence interval (CI) 1.01-1.47) and NPY (rs16139; P=0.034; OR C allele=0.73, 95% CI 0.55-0.97), constituting a direct replication of previously identified SNPs. At the gene level, TNF (rs76917; OR T=1.35, 95% CI 1.13-1.63; P=0.0034) was identified as the only gene for which the association with MDD remained significant after correction for multiple testing. For SLC6A2 (norepinephrine transporter (NET)) significantly more SNPs (19 out of 100; P=0.039) than expected were associated while accounting for the linkage disequilibrium (LD) structure. Thus, we found support for involvement in MDD for only four genes. However, given the number of candidate SNPs and genes that were tested, even these significant may well be false positives. The poor replication may point to publication bias and false-positive findings in previous candidate gene studies, and may also be related to heterogeneity of the MDD phenotype as well as contextual genetic or environmental factors. [ABSTRACT FROM AUTHOR]
Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
FullText Links:
  – Type: pdflink
Text:
  Availability: 0
Header DbId: pbh
DbLabel: Psychology and Behavioral Sciences Collection
An: 60136578
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Poor replication of candidate genes for major depressive disorder using genome-wide association data.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Bosker%2C+F%2E+J%2E%22">Bosker, F. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Hartman%2C+C%2E+A%2E%22">Hartman, C. A.</searchLink><br /><searchLink fieldCode="AR" term="%22Nolte%2C+I%2E+M%2E%22">Nolte, I. M.</searchLink><br /><searchLink fieldCode="AR" term="%22Prins%2C+B%2E+P%2E%22">Prins, B. P.</searchLink><br /><searchLink fieldCode="AR" term="%22Terpstra%2C+P%2E%22">Terpstra, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Posthuma%2C+D%2E%22">Posthuma, D.</searchLink><br /><searchLink fieldCode="AR" term="%22van+Veen%2C+T%2E%22">van Veen, T.</searchLink><br /><searchLink fieldCode="AR" term="%22Willemsen%2C+G%2E%22">Willemsen, G.</searchLink><br /><searchLink fieldCode="AR" term="%22DeRijk%2C+R%2E+H%2E%22">DeRijk, R. H.</searchLink><br /><searchLink fieldCode="AR" term="%22de+Geus%2C+E%2E+J%2E%22">de Geus, E. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Hoogendijk%2C+W%2E+J%2E%22">Hoogendijk, W. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Sullivan%2C+P%2E+F%2E%22">Sullivan, P. F.</searchLink><br /><searchLink fieldCode="AR" term="%22Penninx%2C+B%2E+W%2E%22">Penninx, B. W.</searchLink><br /><searchLink fieldCode="AR" term="%22Boomsma%2C+D%2E+I%2E%22">Boomsma, D. I.</searchLink><br /><searchLink fieldCode="AR" term="%22Snieder%2C+H%2E%22">Snieder, H.</searchLink><br /><searchLink fieldCode="AR" term="%22Nolen%2C+W%2E+A%2E%22">Nolen, W. A.</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. May2011, Vol. 16 Issue 5, p516-532. 17p. 1 Diagram, 3 Charts, 3 Graphs.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+replication%22">DNA replication</searchLink><br /><searchLink fieldCode="DE" term="%22Genes%22">Genes</searchLink><br /><searchLink fieldCode="DE" term="%22Genotype-environment+interaction%22">Genotype-environment interaction</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Data from the Genetic Association Information Network (GAIN) genome-wide association study (GWAS) in major depressive disorder (MDD) were used to explore previously reported candidate gene and single-nucleotide polymorphism (SNP) associations in MDD. A systematic literature search of candidate genes associated with MDD in case-control studies was performed before the results of the GAIN MDD study became available. Measured and imputed candidate SNPs and genes were tested in the GAIN MDD study encompassing 1738 cases and 1802 controls. Imputation was used to increase the number of SNPs from the GWAS and to improve coverage of SNPs in the candidate genes selected. Tests were carried out for individual SNPs and the entire gene using different statistical approaches, with permutation analysis as the final arbiter. In all, 78 papers reporting on 57 genes were identified, from which 92 SNPs could be mapped. In the GAIN MDD study, two SNPs were associated with MDD: C5orf20 (rs12520799; P=0.038; odds ratio (OR) AT=1.10, 95% CI 0.95-1.29; OR TT=1.21, 95% confidence interval (CI) 1.01-1.47) and NPY (rs16139; P=0.034; OR C allele=0.73, 95% CI 0.55-0.97), constituting a direct replication of previously identified SNPs. At the gene level, TNF (rs76917; OR T=1.35, 95% CI 1.13-1.63; P=0.0034) was identified as the only gene for which the association with MDD remained significant after correction for multiple testing. For SLC6A2 (norepinephrine transporter (NET)) significantly more SNPs (19 out of 100; P=0.039) than expected were associated while accounting for the linkage disequilibrium (LD) structure. Thus, we found support for involvement in MDD for only four genes. However, given the number of candidate SNPs and genes that were tested, even these significant may well be false positives. The poor replication may point to publication bias and false-positive findings in previous candidate gene studies, and may also be related to heterogeneity of the MDD phenotype as well as contextual genetic or environmental factors. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=60136578
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1038/mp.2010.38
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 17
        StartPage: 516
    Subjects:
      – SubjectFull: Mental depression
        Type: general
      – SubjectFull: Genetic polymorphisms
        Type: general
      – SubjectFull: DNA replication
        Type: general
      – SubjectFull: Genes
        Type: general
      – SubjectFull: Genotype-environment interaction
        Type: general
    Titles:
      – TitleFull: Poor replication of candidate genes for major depressive disorder using genome-wide association data.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Bosker, F. J.
      – PersonEntity:
          Name:
            NameFull: Hartman, C. A.
      – PersonEntity:
          Name:
            NameFull: Nolte, I. M.
      – PersonEntity:
          Name:
            NameFull: Prins, B. P.
      – PersonEntity:
          Name:
            NameFull: Terpstra, P.
      – PersonEntity:
          Name:
            NameFull: Posthuma, D.
      – PersonEntity:
          Name:
            NameFull: van Veen, T.
      – PersonEntity:
          Name:
            NameFull: Willemsen, G.
      – PersonEntity:
          Name:
            NameFull: DeRijk, R. H.
      – PersonEntity:
          Name:
            NameFull: de Geus, E. J.
      – PersonEntity:
          Name:
            NameFull: Hoogendijk, W. J.
      – PersonEntity:
          Name:
            NameFull: Sullivan, P. F.
      – PersonEntity:
          Name:
            NameFull: Penninx, B. W.
      – PersonEntity:
          Name:
            NameFull: Boomsma, D. I.
      – PersonEntity:
          Name:
            NameFull: Snieder, H.
      – PersonEntity:
          Name:
            NameFull: Nolen, W. A.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 05
              Text: May2011
              Type: published
              Y: 2011
          Identifiers:
            – Type: issn-print
              Value: 13594184
          Numbering:
            – Type: volume
              Value: 16
            – Type: issue
              Value: 5
          Titles:
            – TitleFull: Molecular Psychiatry
              Type: main
ResultId 1