Copy Number Variations in DISC1 and DISC1-Interacting Partners in Major Mental Illness

Mandy Johnstone, Alan Maclean, Lien Heyrman, An-Sofie Lenaerts, Annelie Nordin, Lars-Göran Nilsson, Peter De Rijk, Dirk Goossens, Rolf Adolfsson, David M St Clair, Jeremy Hall, Stephen M Lawrie, Andrew M McIntosh, Jurgen Del-Favero, Douglas H R Blackwood, Benjamin S Pickard

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Abstract

Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification. Here, we report the finding of rare CNVs in DISC1, NDE1 (together with adjacent genes within the 16p13.11 duplication), NDEL1 (including the overlapping MYH10 gene) and CIT. Our findings provide further evidence for involvement of DISC1 and its interaction partners in neuropsychiatric disorders and also for a role of structural variants in the aetiology of these devastating diseases.

Original languageEnglish
Pages (from-to)175-190
Number of pages16
JournalJournal of Neuropsychiatry and Clinical Neurosciences
Volume1
Issue number3
Early online date15 Oct 2015
DOIs
Publication statusPublished - Oct 2015

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Overlapping Genes
Protein Binding
Psychiatry
Population
Genes
Neurodevelopmental Disorders

Keywords

  • copy number variants
  • DISC1
  • NDE1
  • NDEL1
  • Schizophrenia
  • affective disorder
  • intellectual disability

Cite this

Johnstone, M., Maclean, A., Heyrman, L., Lenaerts, A-S., Nordin, A., Nilsson, L-G., ... Pickard, B. S. (2015). Copy Number Variations in DISC1 and DISC1-Interacting Partners in Major Mental Illness. Journal of Neuropsychiatry and Clinical Neurosciences, 1(3), 175-190. https://doi.org/10.1159/000438788

Copy Number Variations in DISC1 and DISC1-Interacting Partners in Major Mental Illness. / Johnstone, Mandy; Maclean, Alan; Heyrman, Lien; Lenaerts, An-Sofie; Nordin, Annelie; Nilsson, Lars-Göran; De Rijk, Peter; Goossens, Dirk; Adolfsson, Rolf; St Clair, David M; Hall, Jeremy; Lawrie, Stephen M; McIntosh, Andrew M; Del-Favero, Jurgen; Blackwood, Douglas H R; Pickard, Benjamin S.

In: Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 1, No. 3, 10.2015, p. 175-190.

Research output: Contribution to journalArticle

Johnstone, M, Maclean, A, Heyrman, L, Lenaerts, A-S, Nordin, A, Nilsson, L-G, De Rijk, P, Goossens, D, Adolfsson, R, St Clair, DM, Hall, J, Lawrie, SM, McIntosh, AM, Del-Favero, J, Blackwood, DHR & Pickard, BS 2015, 'Copy Number Variations in DISC1 and DISC1-Interacting Partners in Major Mental Illness' Journal of Neuropsychiatry and Clinical Neurosciences, vol. 1, no. 3, pp. 175-190. https://doi.org/10.1159/000438788
Johnstone, Mandy ; Maclean, Alan ; Heyrman, Lien ; Lenaerts, An-Sofie ; Nordin, Annelie ; Nilsson, Lars-Göran ; De Rijk, Peter ; Goossens, Dirk ; Adolfsson, Rolf ; St Clair, David M ; Hall, Jeremy ; Lawrie, Stephen M ; McIntosh, Andrew M ; Del-Favero, Jurgen ; Blackwood, Douglas H R ; Pickard, Benjamin S. / Copy Number Variations in DISC1 and DISC1-Interacting Partners in Major Mental Illness. In: Journal of Neuropsychiatry and Clinical Neurosciences. 2015 ; Vol. 1, No. 3. pp. 175-190.
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abstract = "Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification. Here, we report the finding of rare CNVs in DISC1, NDE1 (together with adjacent genes within the 16p13.11 duplication), NDEL1 (including the overlapping MYH10 gene) and CIT. Our findings provide further evidence for involvement of DISC1 and its interaction partners in neuropsychiatric disorders and also for a role of structural variants in the aetiology of these devastating diseases.",
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note = "Acknowledgements We would like to thank all of the patients, relatives and control individuals who participated in the study. We are indebted to the late Prof. Walter Muir, Chair of Developmental Psychiatry and Honorary Consultant in Learning Disability Psychiatry, University of Edinburgh, who initiated these studies and whose work was dedicated to the welfare of the patients who generously participated. We are also grateful to Mrs. Pat Malloy for her assistance with DNA collection and MAQ assays screening of the Scottish samples. The Scottish sample collection was supported by a grant from the Chief Scientist Office (CSO), part of the Scottish Government Health and Social Care Directorates. This research was funded by grants from the CSO to B.S.P. (grant CZB/4/610), The Academy of Medical Sciences/Wellcome Trust to M.J. (grant R41455) and The RS Macdonald Charitable Trust (grant D21419 together with J.H.), the Swedish Research Council (grants 2003-5158 and 2006-4472), the Medical Faculty, Ume{\aa} University, and the County Councils of V{\"a}sterbotten and Norrbotten, Sweden, as well as by grants from the Fund for Scientific Research Flanders (FWO-F), the Industrial Research Fund (IWT) and the Special Research Fund of the University of Antwerp, Belgium. M.J. is funded by a Wellcome Trust Clinical Research Fellowship for MB PhD graduates (R42811). We acknowledge the contribution of the personnel of the VIB Genetic Service Facility (http://www.vibgeneticservicefacility.be/) for the genetic analysis of the Swedish samples. Research nurses Gunnel Johansson, Lotta Kronberg, Tage Johansson and Lisbeth Bertilsson are thankfully acknowledged for their help and expertise. The Betula Study was funded by the Swedish Research Council (grants 345-2003-3883 and 315-2004-6977). We also acknowledge the contribution by the staff in the Betula project",
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T1 - Copy Number Variations in DISC1 and DISC1-Interacting Partners in Major Mental Illness

AU - Johnstone, Mandy

AU - Maclean, Alan

AU - Heyrman, Lien

AU - Lenaerts, An-Sofie

AU - Nordin, Annelie

AU - Nilsson, Lars-Göran

AU - De Rijk, Peter

AU - Goossens, Dirk

AU - Adolfsson, Rolf

AU - St Clair, David M

AU - Hall, Jeremy

AU - Lawrie, Stephen M

AU - McIntosh, Andrew M

AU - Del-Favero, Jurgen

AU - Blackwood, Douglas H R

AU - Pickard, Benjamin S

N1 - Acknowledgements We would like to thank all of the patients, relatives and control individuals who participated in the study. We are indebted to the late Prof. Walter Muir, Chair of Developmental Psychiatry and Honorary Consultant in Learning Disability Psychiatry, University of Edinburgh, who initiated these studies and whose work was dedicated to the welfare of the patients who generously participated. We are also grateful to Mrs. Pat Malloy for her assistance with DNA collection and MAQ assays screening of the Scottish samples. The Scottish sample collection was supported by a grant from the Chief Scientist Office (CSO), part of the Scottish Government Health and Social Care Directorates. This research was funded by grants from the CSO to B.S.P. (grant CZB/4/610), The Academy of Medical Sciences/Wellcome Trust to M.J. (grant R41455) and The RS Macdonald Charitable Trust (grant D21419 together with J.H.), the Swedish Research Council (grants 2003-5158 and 2006-4472), the Medical Faculty, Umeå University, and the County Councils of Västerbotten and Norrbotten, Sweden, as well as by grants from the Fund for Scientific Research Flanders (FWO-F), the Industrial Research Fund (IWT) and the Special Research Fund of the University of Antwerp, Belgium. M.J. is funded by a Wellcome Trust Clinical Research Fellowship for MB PhD graduates (R42811). We acknowledge the contribution of the personnel of the VIB Genetic Service Facility (http://www.vibgeneticservicefacility.be/) for the genetic analysis of the Swedish samples. Research nurses Gunnel Johansson, Lotta Kronberg, Tage Johansson and Lisbeth Bertilsson are thankfully acknowledged for their help and expertise. The Betula Study was funded by the Swedish Research Council (grants 345-2003-3883 and 315-2004-6977). We also acknowledge the contribution by the staff in the Betula project

PY - 2015/10

Y1 - 2015/10

N2 - Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification. Here, we report the finding of rare CNVs in DISC1, NDE1 (together with adjacent genes within the 16p13.11 duplication), NDEL1 (including the overlapping MYH10 gene) and CIT. Our findings provide further evidence for involvement of DISC1 and its interaction partners in neuropsychiatric disorders and also for a role of structural variants in the aetiology of these devastating diseases.

AB - Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification. Here, we report the finding of rare CNVs in DISC1, NDE1 (together with adjacent genes within the 16p13.11 duplication), NDEL1 (including the overlapping MYH10 gene) and CIT. Our findings provide further evidence for involvement of DISC1 and its interaction partners in neuropsychiatric disorders and also for a role of structural variants in the aetiology of these devastating diseases.

KW - copy number variants

KW - DISC1

KW - NDE1

KW - NDEL1

KW - Schizophrenia

KW - affective disorder

KW - intellectual disability

U2 - 10.1159/000438788

DO - 10.1159/000438788

M3 - Article

VL - 1

SP - 175

EP - 190

JO - Journal of Neuropsychiatry and Clinical Neurosciences

JF - Journal of Neuropsychiatry and Clinical Neurosciences

SN - 0895-0172

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ER -