Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression

Pernille Koefoed, David Paul Drucker Woldbye, Thomas van Overeem Hansen, Lene Falgaard Eplov, Søren Hofman Christiansen, Ole Mors, Lars Kessing, Thomas Werge, Katja Kaipio, Ullamari Personen, Thomas Fahmy, Erling Thyge Mellerup, Klaus Damgaard Jakobsen, Elsebeth Hansen, Gitte Moos Knudsen, Jens Otto Drachmann Bukh, Camilla Bock, Camilla Lindberg, Ann Suhl Kristensen, Ole Henrik DamMerete Nordentoft, Thomas Damm Als, August G. Wang, Ulrik Gether, Jens F. Rehfeld, Tom Gert Bolwig

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalActa Neuropsychiatrica
Issue number2
Publication statusPublished - 2012


  • candidate gene approach
  • case-control association study
  • NPY Leu7Proo
  • major depression


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