Association analyses of depression and genes in the hypothalamus-pituitary-adrenal axis.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
The results indicate that ACE could be a potential candidate gene for depression.
1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus University,Risskov,Denmark.
Henrietta Nørmølle
HN
Buttenschøn
3Mental Health Center Copenhagen,Mental Health Services in Capital Region,University of Copenhagen,Copenhagen,Denmark.
Jesper
J
Krogh
1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus University,Risskov,Denmark.
Marit Nyholm
MN
Nielsen
4Research Unit of Clinical Epidemiology,Institute of Clinical Research,University of Southern Denmark,Odense,Denmark.
Linda
L
Kaerlev
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH),Aarhus,Denmark.
Merete
M
Nordentoft
2The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH),Aarhus,Denmark.
Ole
O
Mors
D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010913:Pituitary-Adrenal System / Q000201:enzymology / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
D007703:Peptidyl-Dipeptidase A
angiotensin converting enzyme (ACE); association; depression; hypothalamus–pituitary–adrenal (HPA) axis; single nucleotide polymorphism (SNP)