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Association analyses of depression and genes in the hypothalamus–pituitary–adrenal axis

  • Henrietta Nørmølle Buttenschøn (a1) (a2), Jesper Krogh (a3), Marit Nyholm Nielsen (a1) (a2), Linda Kaerlev (a4) (a5), Merete Nordentoft (a2) (a3) and Ole Mors (a2) (a6)...



Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme (ACE).


In total, 78 single nucleotide polymorphisms (SNPs) and one insertion/deletion polymorphism were genotyped. The study included 408 individuals with depression and 289 controls. In a subset of cases, the interaction between genetic variants and stressful life events (SLEs) was investigated.


After quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated with depression. One nominally significant interaction, most likely due to chance, was identified.


The results indicate that ACE could be a potential candidate gene for depression.


Corresponding author

Henriette Nørmølle Buttenschøn, Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Skovagervej 2, 8240 Risskov, Denmark. Tel: +45 78471163; Fax: +45 78471108; E-mail:


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