Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale

A meta-analysis of genome-wide association studies

A. Demirkan, J. Lahti, N. Direk, A. Viktorin, K. L. Lunetta, A. Terracciano, M. A. Nalls, T. Tanaka, K. Hek, M. Fornage, J. Wellmann, M. C. Cornelis, H. M. Ollila, L. Yu, J. A. Smith, L. C. Pilling, A. Isaacs, A. Palotie, W. V. Zhuang, A. Zonderman & 37 others J. D. Faul, A. Sutin, O. Meirelles, A. Mulas, A. Hofman, A. Uitterlinden, F. Rivadeneira, M. Perola, W. Zhao, V. Salomaa, K. Yaffe, A. I. Luik, Y. Liu, J. Ding, P. Lichtenstein, M. Landén, E. Widen, D. R. Weir, D. J. Llewellyn, A. Murray, S. L R Kardia, J. G. Eriksson, K. Koenen, P. K E Magnusson, L. Ferrucci, T. H. Mosley, F. Cucca, B. A. Oostra, D. A. Bennett, T. Paunio, K. Berger, T. B. Harris, N. L. Pedersen, J. M. Murabito, H. Tiemeier, C. M. Van Duijn, K. Räikkönen

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Background Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. Method We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). Results One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. Conclusions Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

    Original languageEnglish
    Pages (from-to)1613-1623
    Number of pages11
    JournalPsychological Medicine
    Volume46
    Issue number8
    DOIs
    StatePublished - Jun 1 2016

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    Genome-Wide Association Study
    Meta-Analysis
    Epidemiologic Studies
    Depression
    Major Depressive Disorder
    Single Nucleotide Polymorphism
    Melatonin Receptors
    Genome
    Phenotype
    Brain
    Genes

    All Science Journal Classification (ASJC) codes

    • Psychiatry and Mental health
    • Applied Psychology

    Cite this

    Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale : A meta-analysis of genome-wide association studies. / Demirkan, A.; Lahti, J.; Direk, N.; Viktorin, A.; Lunetta, K. L.; Terracciano, A.; Nalls, M. A.; Tanaka, T.; Hek, K.; Fornage, M.; Wellmann, J.; Cornelis, M. C.; Ollila, H. M.; Yu, L.; Smith, J. A.; Pilling, L. C.; Isaacs, A.; Palotie, A.; Zhuang, W. V.; Zonderman, A.; Faul, J. D.; Sutin, A.; Meirelles, O.; Mulas, A.; Hofman, A.; Uitterlinden, A.; Rivadeneira, F.; Perola, M.; Zhao, W.; Salomaa, V.; Yaffe, K.; Luik, A. I.; Liu, Y.; Ding, J.; Lichtenstein, P.; Landén, M.; Widen, E.; Weir, D. R.; Llewellyn, D. J.; Murray, A.; Kardia, S. L R; Eriksson, J. G.; Koenen, K.; Magnusson, P. K E; Ferrucci, L.; Mosley, T. H.; Cucca, F.; Oostra, B. A.; Bennett, D. A.; Paunio, T.; Berger, K.; Harris, T. B.; Pedersen, N. L.; Murabito, J. M.; Tiemeier, H.; Van Duijn, C. M.; Räikkönen, K.

    In: Psychological Medicine, Vol. 46, No. 8, 01.06.2016, p. 1613-1623.

    Research output: Contribution to journalArticle

    Demirkan, A, Lahti, J, Direk, N, Viktorin, A, Lunetta, KL, Terracciano, A, Nalls, MA, Tanaka, T, Hek, K, Fornage, M, Wellmann, J, Cornelis, MC, Ollila, HM, Yu, L, Smith, JA, Pilling, LC, Isaacs, A, Palotie, A, Zhuang, WV, Zonderman, A, Faul, JD, Sutin, A, Meirelles, O, Mulas, A, Hofman, A, Uitterlinden, A, Rivadeneira, F, Perola, M, Zhao, W, Salomaa, V, Yaffe, K, Luik, AI, Liu, Y, Ding, J, Lichtenstein, P, Landén, M, Widen, E, Weir, DR, Llewellyn, DJ, Murray, A, Kardia, SLR, Eriksson, JG, Koenen, K, Magnusson, PKE, Ferrucci, L, Mosley, TH, Cucca, F, Oostra, BA, Bennett, DA, Paunio, T, Berger, K, Harris, TB, Pedersen, NL, Murabito, JM, Tiemeier, H, Van Duijn, CM & Räikkönen, K 2016, 'Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: A meta-analysis of genome-wide association studies', Psychological Medicine, vol. 46, no. 8, pp. 1613-1623. https://doi.org/10.1017/S0033291715002081
    Demirkan, A. ; Lahti, J. ; Direk, N. ; Viktorin, A. ; Lunetta, K. L. ; Terracciano, A. ; Nalls, M. A. ; Tanaka, T. ; Hek, K. ; Fornage, M. ; Wellmann, J. ; Cornelis, M. C. ; Ollila, H. M. ; Yu, L. ; Smith, J. A. ; Pilling, L. C. ; Isaacs, A. ; Palotie, A. ; Zhuang, W. V. ; Zonderman, A. ; Faul, J. D. ; Sutin, A. ; Meirelles, O. ; Mulas, A. ; Hofman, A. ; Uitterlinden, A. ; Rivadeneira, F. ; Perola, M. ; Zhao, W. ; Salomaa, V. ; Yaffe, K. ; Luik, A. I. ; Liu, Y. ; Ding, J. ; Lichtenstein, P. ; Landén, M. ; Widen, E. ; Weir, D. R. ; Llewellyn, D. J. ; Murray, A. ; Kardia, S. L R ; Eriksson, J. G. ; Koenen, K. ; Magnusson, P. K E ; Ferrucci, L. ; Mosley, T. H. ; Cucca, F. ; Oostra, B. A. ; Bennett, D. A. ; Paunio, T. ; Berger, K. ; Harris, T. B. ; Pedersen, N. L. ; Murabito, J. M. ; Tiemeier, H. ; Van Duijn, C. M. ; Räikkönen, K. / Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale : A meta-analysis of genome-wide association studies. In: Psychological Medicine. 2016 ; Vol. 46, No. 8. pp. 1613-1623.
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    title = "Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: A meta-analysis of genome-wide association studies",
    abstract = "Background Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. Method We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). Results One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. Conclusions Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.",
    author = "A. Demirkan and J. Lahti and N. Direk and A. Viktorin and Lunetta, {K. L.} and A. Terracciano and Nalls, {M. A.} and T. Tanaka and K. Hek and M. Fornage and J. Wellmann and Cornelis, {M. C.} and Ollila, {H. M.} and L. Yu and Smith, {J. A.} and Pilling, {L. C.} and A. Isaacs and A. Palotie and Zhuang, {W. V.} and A. Zonderman and Faul, {J. D.} and A. Sutin and O. Meirelles and A. Mulas and A. Hofman and A. Uitterlinden and F. Rivadeneira and M. Perola and W. Zhao and V. Salomaa and K. Yaffe and Luik, {A. I.} and Y. Liu and J. Ding and P. Lichtenstein and M. Land{\'e}n and E. Widen and Weir, {D. R.} and Llewellyn, {D. J.} and A. Murray and Kardia, {S. L R} and Eriksson, {J. G.} and K. Koenen and Magnusson, {P. K E} and L. Ferrucci and Mosley, {T. H.} and F. Cucca and Oostra, {B. A.} and Bennett, {D. A.} and T. Paunio and K. Berger and Harris, {T. B.} and Pedersen, {N. L.} and Murabito, {J. M.} and H. Tiemeier and {Van Duijn}, {C. M.} and K. R{\"a}ikk{\"o}nen",
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    TY - JOUR

    T1 - Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale

    T2 - A meta-analysis of genome-wide association studies

    AU - Demirkan, A.

    AU - Lahti, J.

    AU - Direk, N.

    AU - Viktorin, A.

    AU - Lunetta, K. L.

    AU - Terracciano, A.

    AU - Nalls, M. A.

    AU - Tanaka, T.

    AU - Hek, K.

    AU - Fornage, M.

    AU - Wellmann, J.

    AU - Cornelis, M. C.

    AU - Ollila, H. M.

    AU - Yu, L.

    AU - Smith, J. A.

    AU - Pilling, L. C.

    AU - Isaacs, A.

    AU - Palotie, A.

    AU - Zhuang, W. V.

    AU - Zonderman, A.

    AU - Faul, J. D.

    AU - Sutin, A.

    AU - Meirelles, O.

    AU - Mulas, A.

    AU - Hofman, A.

    AU - Uitterlinden, A.

    AU - Rivadeneira, F.

    AU - Perola, M.

    AU - Zhao, W.

    AU - Salomaa, V.

    AU - Yaffe, K.

    AU - Luik, A. I.

    AU - Liu, Y.

    AU - Ding, J.

    AU - Lichtenstein, P.

    AU - Landén, M.

    AU - Widen, E.

    AU - Weir, D. R.

    AU - Llewellyn, D. J.

    AU - Murray, A.

    AU - Kardia, S. L R

    AU - Eriksson, J. G.

    AU - Koenen, K.

    AU - Magnusson, P. K E

    AU - Ferrucci, L.

    AU - Mosley, T. H.

    AU - Cucca, F.

    AU - Oostra, B. A.

    AU - Bennett, D. A.

    AU - Paunio, T.

    AU - Berger, K.

    AU - Harris, T. B.

    AU - Pedersen, N. L.

    AU - Murabito, J. M.

    AU - Tiemeier, H.

    AU - Van Duijn, C. M.

    AU - Räikkönen, K.

    PY - 2016/6/1

    Y1 - 2016/6/1

    N2 - Background Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. Method We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). Results One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. Conclusions Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

    AB - Background Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. Method We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). Results One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. Conclusions Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

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