Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression
Corresponding Author
Pernille Koefoed
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Both authors contributed equally.
Pernille Koefoed, Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen & Mental Health Centre Copenhagen, Rigshospitalet O-6102, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.Tel.: +45 3545 6113;Fax: +45 3539 3546;E-mail: [email protected]Search for more papers by this authorDavid P.D. Woldbye
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Both authors contributed equally.
Search for more papers by this authorThomas v. O. Hansen
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorLene F. Eplov
Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark and Research Unit for Psychiatric Rehabilitation, Mental Health Centre Ballerup, Ballerup, Denmark
Search for more papers by this authorSøren H. Christiansen
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorOle Mors
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
Search for more papers by this authorLars V. Kessing
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorThomas Werge
Research Institute of Biological Psychiatry, Mental Health Centre St. Hans Hospital, Roskilde, Denmark
Search for more papers by this authorKatja Kaipio
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Search for more papers by this authorUllamari Pesonen
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Search for more papers by this authorThomas Fahmy
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorErling Mellerup
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorKlaus D. Jakobsen
Research Institute of Biological Psychiatry, Mental Health Centre St. Hans Hospital, Roskilde, Denmark
Mental Health Centre Hvidovre, Hvidovre, Denmark
Search for more papers by this authorElsebeth S. Hansen
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorGitte M. Knudsen
Center for Integrated Molecular Brain Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorJens D. Bukh
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorCamilla Bock
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorCamilla Lindberg
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorAnn S. Kristensen
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
Search for more papers by this authorHenrik Dam
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorMerete Nordentoft
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorThomas D. Als
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
Search for more papers by this authorAugust G. Wang
Mental Health Centre Amager, Copenhagen, Denmark
Search for more papers by this authorUlrik Gether
Molecular Neuropharmacology Group and Center for Pharmacogenomics, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorJens F. Rehfeld
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorTom G. Bolwig
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorCorresponding Author
Pernille Koefoed
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Both authors contributed equally.
Pernille Koefoed, Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen & Mental Health Centre Copenhagen, Rigshospitalet O-6102, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.Tel.: +45 3545 6113;Fax: +45 3539 3546;E-mail: [email protected]Search for more papers by this authorDavid P.D. Woldbye
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Both authors contributed equally.
Search for more papers by this authorThomas v. O. Hansen
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorLene F. Eplov
Research Centre for Prevention and Health, Copenhagen University Hospital Glostrup, Glostrup, Denmark and Research Unit for Psychiatric Rehabilitation, Mental Health Centre Ballerup, Ballerup, Denmark
Search for more papers by this authorSøren H. Christiansen
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorOle Mors
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
Search for more papers by this authorLars V. Kessing
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorThomas Werge
Research Institute of Biological Psychiatry, Mental Health Centre St. Hans Hospital, Roskilde, Denmark
Search for more papers by this authorKatja Kaipio
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Search for more papers by this authorUllamari Pesonen
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland
Search for more papers by this authorThomas Fahmy
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorErling Mellerup
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorKlaus D. Jakobsen
Research Institute of Biological Psychiatry, Mental Health Centre St. Hans Hospital, Roskilde, Denmark
Mental Health Centre Hvidovre, Hvidovre, Denmark
Search for more papers by this authorElsebeth S. Hansen
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorGitte M. Knudsen
Center for Integrated Molecular Brain Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorJens D. Bukh
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorCamilla Bock
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorCamilla Lindberg
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorAnn S. Kristensen
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
Search for more papers by this authorHenrik Dam
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorMerete Nordentoft
Mental Health Centre Copenhagen, Rigshospitalet, Copenhagen, Denmark
Search for more papers by this authorThomas D. Als
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
Search for more papers by this authorAugust G. Wang
Mental Health Centre Amager, Copenhagen, Denmark
Search for more papers by this authorUlrik Gether
Molecular Neuropharmacology Group and Center for Pharmacogenomics, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorJens F. Rehfeld
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorTom G. Bolwig
Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorAbstract
Koefoed P, Woldbye DPD, Hansen TvO, Eplov LF, Christiansen SH, Mors O, Kessing LV, Werge T, Kaipio K, Pesonen U, Fahmy T, Mellerup E, Jakobsen KD, Hansen ES, Knudsen GM, Bukh JD, Bock C, Lindberg C, Kristensen AS, Dam H, Nordentoft M, Als TD, Wang AG, Gether U, Rehfeld JF, Bolwig TG. Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression.
Objective: There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression.
Method: Leu7Pro was studied in a sample of depressed patients and ethnically matched controls, as well as psychiatric disease controls with schizophrenia. Possible functional consequences of Leu7Pro were explored in vitro.
Results: In contrast to previous studies, Pro7 appeared to be a risk allele for depression, being significantly more frequent in the depression sample (5.5%, n = 593; p = 0.009; odds ratio, OR: 1.46) as compared to ethnically matched controls (3.8%, n = 2912), while schizophrenia patients (4.1%, n = 503) did not differ. In vitro, the Pro7 substitution appeared to be associated with reduced levels of NPY without affecting its mRNA level.
Conclusion: The Leu7Pro variation may increase the risk of major depression, possibly by affecting the biosynthesis of NPY.
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